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Mar. Drugs, Volume 23, Issue 1 (January 2025) – 43 articles

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17 pages, 1859 KiB  
Systematic Review
Exploring Antibacterial Properties of Marine Sponge-Derived Natural Compounds: A Systematic Review
by Cintia Cristina Santi Martignago, Camila de Souza Barbosa, Homero Garcia Motta, Beatriz Soares-Silva, Erica Paloma Maso Lopes Peres, Lais Caroline Souza e Silva, Mirian Bonifácio, Karolyne dos Santos Jorge Sousa, Amanda Sardeli Alqualo, Júlia Parisi, Olivier Jordan, Ana Claudia Muniz Renno, Anna Caroline Campos Aguiar and Viorica Patrulea
Mar. Drugs 2025, 23(1), 43; https://doi.org/10.3390/md23010043 - 16 Jan 2025
Viewed by 116
Abstract
The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring [...] Read more.
The rise in multidrug-resistant (MDR) bacteria has prompted extensive research into antibacterial compounds, as these resistant strains compromise current treatments. This resistance leads to prolonged hospitalization, increased mortality rates, and higher healthcare costs. To address this challenge, the pharmaceutical industry is increasingly exploring natural products, particularly those of marine origin, as promising candidates for antimicrobial drugs. Marine sponges, in particular, are of interest because of their production of secondary metabolites (SM), which serve as chemical defenses against predators and pathogens. These metabolites exhibit a wide range of therapeutic properties, including antibacterial activity. This systematic review examines recent advancements in identifying new sponge-derived compounds with antimicrobial activity, specifically targeting Pseudomonas aeruginosa, a prevalent Gram-negative pathogen with the highest incidence rates in clinical settings. The selection criteria focused on antimicrobial compounds with reported Minimum Inhibitory Concentration (MIC) values. The identified SM include alkaloids, sesterterpenoids, nitrogenous diterpene, and bromotyrosine-derived derivatives. The structural features of the active compounds selected in this review may provide a foundational framework for developing new, highly bioactive antimicrobial agents. Full article
(This article belongs to the Special Issue Marine Natural Products with Antimicrobial Activity)
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<p>PRISMA Flow diagram of the search strategy used in the present study.</p>
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<p>General structure of tetracyclic alkylpiperidine alkaloids. The * indicates the chiral center in the molecule.</p>
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<p>General structures of bisindole alkaloids. The * indicates the chiral center in the molecules.</p>
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<p>The general structure of scalarane alkaloids.</p>
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<p>The general structure of bromopyrrole and imidazole-containing alkaloids.</p>
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<p>Example of agelasine- and agelasidine-type alkaloids isolated from <span class="html-italic">Agelas</span> sponges.</p>
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<p>The general structure of ianthelliformisamine compounds.</p>
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<p>Results of the risk of bias analysis of the studies included in this review.</p>
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24 pages, 4362 KiB  
Article
Optimization of the Extraction Protocol for Pacific Ciguatoxins from Marine Products Prior to Analysis Using the Neuroblastoma Cell-Based Assay
by Thomas Yon, Philippe Cruchet, Jérôme Viallon, J. Sam Murray, Emillie Passfield, Mireille Chinain, Hélène Taiana Darius and Mélanie Roué
Mar. Drugs 2025, 23(1), 42; https://doi.org/10.3390/md23010042 - 16 Jan 2025
Viewed by 190
Abstract
Ciguatera poisoning (CP) is caused by the consumption of marine products contaminated with ciguatoxins (CTXs) produced by dinoflagellates of the genus Gambierdiscus. Analytical methods for CTXs, involving the extraction/purification of trace quantities of CTXs from complex matrices, are numerous in the literature. [...] Read more.
Ciguatera poisoning (CP) is caused by the consumption of marine products contaminated with ciguatoxins (CTXs) produced by dinoflagellates of the genus Gambierdiscus. Analytical methods for CTXs, involving the extraction/purification of trace quantities of CTXs from complex matrices, are numerous in the literature. However, little information on their effectiveness for nonpolar CTXs is available, yet these congeners, contributing to the risk of CP, are required for the establishment of effective food safety monitoring programs. An evaluation of six extraction/purification protocols, performed with CTX3C spiked on fish flesh and a neuroblastoma cell-based assay (CBA-N2a), revealed recoveries from 6 to 45%. This led to the development of an optimized 3-day protocol designed for a large number of samples, with CTX1B and CTX3C eluting in a single fraction and showing recoveries of 73% and 70%, respectively. In addition, a reduction in adverse matrix effects in the CBA-N2a analyses was demonstrated with naturally contaminated specimens, increasing the sensitivity of the method, which now meets the very low guidance level recommended by international agencies. However, efforts are still required to reduce the signal suppression observed in LC-MS/MS analysis. This optimized protocol contributes to the technological advancement of detection methods, promoting food safety and improving CP risk assessment in marine products. Full article
(This article belongs to the Special Issue Commemorating the Launch of the Section "Marine Toxins")
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<p>Schematic representation of the OP protocol with CTX1B and CTX3C amounts (ng) estimated by the CBA-N2a in testable fractions. Data represent the mean ± standard deviation (SD) (each concentration run in triplicate wells) of three independent experiments run on different days. In bold is the CTX pathway through the different steps.</p>
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<p>CTX levels estimated with the CBA-N2a in fractions of interest purified from naturally contaminated fish and shellfish using protocol #1 <span class="html-fig-inline" id="marinedrugs-23-00042-i001"><img alt="Marinedrugs 23 00042 i001" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i001.png"/></span> and the OP protocol <span class="html-fig-inline" id="marinedrugs-23-00042-i002"><img alt="Marinedrugs 23 00042 i002" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i002.png"/></span>. Data represent the mean ± SD (each concentration run in triplicate wells) of three independent experiments run on different days on at least two extraction replicates. The marine products analyzed were for the herbivores (<b>a</b>) steephead parrotfish, <span class="html-italic">Chlorurus microrhinos</span>, (<b>b</b>) yellowfin surgeonfish, <span class="html-italic">Acanthurus xanthopterus</span>, and (<b>c</b>) trochus, <span class="html-italic">Tectus niloticus</span>, and the carnivores (<b>d</b>) giant moray, <span class="html-italic">Gymnothorax javanicus</span>, (<b>e</b>) longface emperor, <span class="html-italic">Lethrinus olivaceus</span>, and (<b>f</b>) bluefin trevally, <span class="html-italic">Caranx melampygus</span>.</p>
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<p>CTX levels estimated with the CBA-N2a in fractions of interest purified from naturally contaminated fish and shellfish using protocol #1 <span class="html-fig-inline" id="marinedrugs-23-00042-i001"><img alt="Marinedrugs 23 00042 i001" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i001.png"/></span> and the OP protocol <span class="html-fig-inline" id="marinedrugs-23-00042-i002"><img alt="Marinedrugs 23 00042 i002" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i002.png"/></span>. Data represent the mean ± SD (each concentration run in triplicate wells) of three independent experiments run on different days on at least two extraction replicates. The marine products analyzed were for the herbivores (<b>a</b>) steephead parrotfish, <span class="html-italic">Chlorurus microrhinos</span>, (<b>b</b>) yellowfin surgeonfish, <span class="html-italic">Acanthurus xanthopterus</span>, and (<b>c</b>) trochus, <span class="html-italic">Tectus niloticus</span>, and the carnivores (<b>d</b>) giant moray, <span class="html-italic">Gymnothorax javanicus</span>, (<b>e</b>) longface emperor, <span class="html-italic">Lethrinus olivaceus</span>, and (<b>f</b>) bluefin trevally, <span class="html-italic">Caranx melampygus</span>.</p>
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<p>Cytotoxic dose–response curves under OV<sup>-</sup> (black circle) and OV<sup>+</sup> (black triangle) conditions obtained using the CBA-N2a on fractions of interest purified from naturally contaminated yellowfin surgeonfish and bluefin trevally samples using protocol #1 (<b>a</b>,<b>b</b>) and the OP protocol (<b>c</b>,<b>d</b>). Data represent the mean ± SD of each concentration run in triplicate wells. Non-specific mortality due to matrix effects is observed above the dotted red line.</p>
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<p>Percentages of signal suppression observed in LC-MS/MS analysis after fortification experiments (spiking extracts with a mix of CTX1B, CTX3B, CTX3C and CTX4A standard solutions) of the (<b>a</b>) steephead parrotfish <span class="html-fig-inline" id="marinedrugs-23-00042-i003"><img alt="Marinedrugs 23 00042 i003" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i003.png"/></span>, marbled grouper <span class="html-fig-inline" id="marinedrugs-23-00042-i004"><img alt="Marinedrugs 23 00042 i004" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i004.png"/></span> and bluefin trevally <span class="html-fig-inline" id="marinedrugs-23-00042-i005"><img alt="Marinedrugs 23 00042 i005" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i005.png"/></span>, obtained with the OP protocol, as well as of the (<b>b</b>) bluefin trevally, obtained with the OP protocol <span class="html-fig-inline" id="marinedrugs-23-00042-i006"><img alt="Marinedrugs 23 00042 i006" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i006.png"/></span>, protocol #1 <span class="html-fig-inline" id="marinedrugs-23-00042-i007"><img alt="Marinedrugs 23 00042 i007" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i007.png"/></span> and the protocol published in Murray et al. [<a href="#B27-marinedrugs-23-00042" class="html-bibr">27</a>] <span class="html-fig-inline" id="marinedrugs-23-00042-i008"><img alt="Marinedrugs 23 00042 i008" src="/marinedrugs/marinedrugs-23-00042/article_deploy/html/images/marinedrugs-23-00042-i008.png"/></span>.</p>
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23 pages, 2860 KiB  
Article
Novel Insights into the Nobilamide Family from a Deep-Sea Bacillus: Chemical Diversity, Biosynthesis and Antimicrobial Activity Towards Multidrug-Resistant Bacteria
by Vincenza Casella, Gerardo Della Sala, Silvia Scarpato, Carmine Buonocore, Costanza Ragozzino, Pietro Tedesco, Daniela Coppola, Giovanni Andrea Vitale, Donatella de Pascale and Fortunato Palma Esposito
Mar. Drugs 2025, 23(1), 41; https://doi.org/10.3390/md23010041 - 14 Jan 2025
Viewed by 497
Abstract
With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection [...] Read more.
With rising concerns about antimicrobial resistance, the identification of new lead compounds to target multidrug-resistant bacteria is essential. This study employed a fast miniaturized screening to simultaneously cultivate and evaluate about 300 marine strains for biosurfactant and antibacterial activities, leading to the selection of the deep-sea Bacillus halotolerans BCP32. The integration of tandem mass spectrometry molecular networking and bioassay-guided fractionation unveiled this strain as a prolific factory of surfactins and nobilamides. Particularly, 84 nobilamide congeners were identified in the bacterial exometabolome, 71 of them being novel metabolites. Among these, four major compounds were isolated, including the known TL-119 and nobilamide I, as well as the two new nobilamides T1 and S1. TL-119 and nobilamide S1 exhibited potent antibiotic activity against various multidrug-resistant Staphylococcus strains and other Gram-positive pathogens, including the foodborne pathogen Listeria monocytogenes. Finally, in silico analysis of Bacillus halotolerans BCP32 genome revealed nobilamide biosynthesis to be directed by a previously unknown heptamodular nonribosomal peptide synthetase. Full article
(This article belongs to the Special Issue Bioactive Natural Products from the Deep-Sea-Sourced Microbes)
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<p>Graphical overview of the primary screening method applied to 300 marine bacteria from the Stazione Zoologica Anton Dohrn library. Bacterial cultures were grown in deep-well plates under various conditions, including different growth media, incubation periods, and temperatures. To evaluate their bioactivities, the CTAB agar assay was used to screen for biosurfactant production, while the agar diffusion well method was employed to assess antimicrobial activity.</p>
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<p>Surfactant activity of F-90% MeOH from <span class="html-italic">Bacillus</span> sp. BCP32 in the oil spreading test. (<b>a</b>) DMSO vehicle (4 μL) was used as negative control; (<b>b</b>) The clear zone on the oil surface indicates the presence of biosurfactants.</p>
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<p>LC-HRMS<sup>2</sup>-based molecular network (MN) of F-90% MeOH from <span class="html-italic">Bacillus</span> sp. BCP32. The MN is dominated by two large clusters, i.e., nobilamides (blue nodes) and surfactins (orange nodes). Compounds are visualized as nodes, and node size reflects the compound peak area. Edge thickness is related to MS<sup>2</sup> spectra similarity. Nobilamides reported in <a href="#marinedrugs-23-00041-f004" class="html-fig">Figure 4</a> and compounds isolated in this study have been annotated in the MN.</p>
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<p>Chemical structures of representative nobilamides from <span class="html-italic">Bacillus</span> sp. BCP32.</p>
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<p>HRMS<sup>2</sup> spectra of the [M + H]<sup>+</sup> pseudomolecular ions of representative cyclic (<b>A</b>) and linear (<b>B</b>) nobilamides from <span class="html-italic">Bacillus</span> sp. BCP32.</p>
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<p>Putative biosynthesis of TL-119. Genes flanking the <span class="html-italic">nbl</span> operon are annotated in <a href="#app1-marinedrugs-23-00041" class="html-app">Table S5</a>. Abbreviations: C, condensation domain; A, adenylation domain; PCP, peptidyl-carrier protein; E, epimerase; TE, thioesterase.</p>
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17 pages, 2531 KiB  
Article
Optimization of a Sonotrode Extraction Method and New Insight of Phenolic Composition of Fucus vesiculosus
by Lidia Gil-Martínez, Alejandro Santos-Mejías, José Manuel De la Torre-Ramírez, Alberto Baños, Vito Verardo and Ana M. Gómez-Caravaca
Mar. Drugs 2025, 23(1), 40; https://doi.org/10.3390/md23010040 - 14 Jan 2025
Viewed by 318
Abstract
The optimization of bioactive compound extraction from Fucus vesiculosus using ultrasound-assisted extraction (UAE) via sonotrode was investigated to maximize phenolic recovery and antioxidant activity while promoting a sustainable process. Optimal conditions (40% v/v ethanol in water, 38 min, 36% amplitude) were [...] Read more.
The optimization of bioactive compound extraction from Fucus vesiculosus using ultrasound-assisted extraction (UAE) via sonotrode was investigated to maximize phenolic recovery and antioxidant activity while promoting a sustainable process. Optimal conditions (40% v/v ethanol in water, 38 min, 36% amplitude) were selected to maximize phenolic recovery while considering environmental and energy sustainability by optimizing extraction efficiency and minimizing solvent and energy usage. HPLC-ESI-QTOF-MS analysis tentatively identified 25 phenolic compounds, including sulfated phenolic acids, phlorotannins, flavonoids, and halophenols, with some reported for the first time in F. vesiculosus, underscoring the complexity of this alga’s metabolome. The antioxidant activity of the optimized extract was evaluated through FRAP (143.7 µmol TE/g), DPPH (EC50 105.6 µg/mL), and TEAC (189.1 µmol Trolox/g) assays. The optimized process highlights F. vesiculosus as a valuable source of natural antioxidants, with potential applications in biotechnology, cosmetics, and food industries. Full article
(This article belongs to the Special Issue Therapeutic Potential of Phlorotannins)
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<p>Response surface plots showing combined effects of process variables for TPC (mg GAE/g dry seaweed.): amplitude (%)–time (min) (<b>a</b>), amplitude (%)–% EtOH (<b>b</b>), and % EtOH–time (min) (<b>c</b>); GAE: Gallic acid equivalents.</p>
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<p>(<b>a</b>) Peak MS/MS spectra of tentatively identified vanillic acid sulfate, showing fragment ions <span class="html-italic">m</span>/<span class="html-italic">z</span> 247, <span class="html-italic">m</span>/<span class="html-italic">z</span> 203, and <span class="html-italic">m</span>/<span class="html-italic">z</span> 123 and presumed fragmentation pattern of the molecule. (<b>b</b>) Peak MS/MS spectra of tentatively identified hydroxytyrosol sulfate, showing fragment ions <span class="html-italic">m</span>/<span class="html-italic">z</span> 233, <span class="html-italic">m</span>/<span class="html-italic">z</span> 153, and <span class="html-italic">m</span>/<span class="html-italic">z</span> 123 and presumed fragmentation pattern of the molecule.</p>
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<p>HRMS spectra of Peak 18, with the proposed molecule of lanosol sulfate indicating the <span class="html-italic">m</span>/<span class="html-italic">z</span> of the fragments (in red), and MS/MS spectrum (in blue).</p>
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<p>HRMS and MS/MS spectra at retention time of 10.883, indicating the proposed fragments for Peak 20 (in red) and the tentative fragments for Peak 21 (in blue).</p>
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<p>HRMS of compound 23, tentatively identified as chlorobenzoic acid (<b>a</b>), compound 24, dichlorophenol (<b>b</b>), compound 25, trichlorophenol (<b>c</b>), and compound 26, tetrachlorophenol (<b>d</b>).</p>
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26 pages, 4179 KiB  
Review
Actinomycete-Derived Pigments: A Path Toward Sustainable Industrial Colorants
by Blanca Hey Díez, Cristiana A. V. Torres and Susana P. Gaudêncio
Mar. Drugs 2025, 23(1), 39; https://doi.org/10.3390/md23010039 - 13 Jan 2025
Viewed by 337
Abstract
Pigment production has a substantial negative impact on the environment, since mining for natural pigments causes ecosystem degradation, while synthetic pigments, derived from petrochemicals, generate toxic by-products that accumulate and persist in aquatic systems due to their resistance to biodegradation. Despite these challenges, [...] Read more.
Pigment production has a substantial negative impact on the environment, since mining for natural pigments causes ecosystem degradation, while synthetic pigments, derived from petrochemicals, generate toxic by-products that accumulate and persist in aquatic systems due to their resistance to biodegradation. Despite these challenges, pigments remain essential across numerous industries, including the cosmetic, textile, food, automotive, paints and coatings, plastics, and packaging industries. In response to growing consumer demand for sustainable options, there is increasing interest in eco-friendly alternatives, particularly bio-based pigments derived from algae, fungi, and actinomycetes. This shift is largely driven by consumer demand for sustainable options. For bio-pigments, actinomycetes, particularly from the Streptomyces genus, have emerged as a promising green source, aligning with global sustainability goals due to their renewability and biodegradability. Scale-up of production and yield optimization challenges have been circumvented with the aid of biotechnology advancements, including genetic engineering and innovative fermentation and extraction methods, which have enhanced these bio-pigments’ viability and cost-competitiveness. Actinomycete-derived pigments have successfully transitioned from laboratory research to commercialization, showcasing their potential as sustainable and eco-friendly alternatives to synthetic dyes. With the global pigment market valued at approximately USD 24.28 billion in 2023, which is projected to reach USD 36.58 billion by 2030, the economic potential for actinomycete pigments is extensive. This review explores the environmental advantages of actinomycete pigments, their role in modern industry, and the regulatory and commercialization challenges they face, highlighting the importance of these pigments as promising solutions to reduce our reliance on conventional toxic pigments. The successful commercialization of actinomycete pigments can drive an industry-wide transition to environmentally responsible alternatives, offering substantial benefits for human health, safety, and environmental sustainability. Full article
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<p>New trends in pigment technology. Created in <a href="https://BioRender.com" target="_blank">https://BioRender.com</a>.</p>
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<p>Pigment production solutions to mitigate environmental impacts. Created in <a href="https://BioRender.com" target="_blank">https://BioRender.com</a>.</p>
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<p>Culture and extraction of bacterial pigments. Created in <a href="https://BioRender.com" target="_blank">https://BioRender.com</a>.</p>
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14 pages, 2676 KiB  
Article
Polysaccharide Fraction Isolated from Saccharina japonica Exhibits Anti-Cancer Effects Through Immunostimulating Activities
by Min Seung Park, Seung-U Son, Tae Eun Kim, Se Hyun Shim, Bong-Keun Jang, Sunyoung Park and Kwang-Soon Shin
Mar. Drugs 2025, 23(1), 38; https://doi.org/10.3390/md23010038 - 13 Jan 2025
Viewed by 503
Abstract
The present research aimed to assess the anti-cancer effects of the polysaccharide fraction (SJP) isolated from Saccharina japonica. The release of immune-activating cytokines, including IL-6, IL-12, and TNF-α, was markedly stimulated by the SJP in a concentration-dependent manner within the range of [...] Read more.
The present research aimed to assess the anti-cancer effects of the polysaccharide fraction (SJP) isolated from Saccharina japonica. The release of immune-activating cytokines, including IL-6, IL-12, and TNF-α, was markedly stimulated by the SJP in a concentration-dependent manner within the range of 1 to 100 µg/mL. Furthermore, the prophylactic intravenous (p.i.v.) and per os (p.p.o.) injection of SJP boosted the cytolytic activity mediated by NK cells and CTLs against tumor cells. In a study involving Colon26-M3.1 carcinoma as a lung cancer model, both p.i.v. and p.p.o. exhibited significant anti-lung-cancer effects. Notably, p.i.v. and p.p.o. administration of SJP at a dose of 50 mg/kg reduced tumor colonies by 84% and 40%, respectively, compared to the control. Moreover, the anti-lung-cancer effects of SJP remained substantial, even when NK cell function was inhibited using anti-asialo-GM1. Fractionation with CaCl2 suggested that SJP is a mixture of alginate and fucoidan. The fucoidan fraction stimulated the immune response of macrophages more strongly than the alginate fraction. Consequently, this finding suggested that SJP from S. japonica possesses remarkable anti-cancer effects through the activation of various immunocytes. In addition, this finding indicates that the potent biological activity of SJP may be attributed to fucoidan. Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 4th Edition)
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<p>Effects of SJP isolated from <span class="html-italic">Saccharina japonica</span> about cytokine release by macrophages. (<b>a</b>) IL-6, (<b>b</b>) IL-12, and (<b>c</b>) TNF-α concentration of culture supernatant. The medium and LPS (1 μg/mL) represent the NC and PC, respectively. All data are presented as the mean ± standard deviation (<span class="html-italic">n</span> = 3); the different letters (a–e) indicate statistical significance (<span class="html-italic">p</span> &lt; 0.05). Significant differences were evaluated using the one-way analysis of variance followed by Duncan’s test for multiple comparisons. NC, negative control; PC, positive control.</p>
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<p>Comparison of NK cell and CTL cytotoxic activity against cancer cells by SJP. (<b>a</b>,<b>b</b>) Cytotoxicity of NK cells and CTLs by <span class="html-italic">i.v.</span> administration. (<b>c</b>,<b>d</b>) Cytotoxicity of NK cells and CTLs by oral administration. NK cells and CTLs were co-cultured with YAC-1 lymphoma and Colon26-M3.1 carcinoma, respectively, for 6 h in a 5% CO<sub>2</sub> incubator at 37 °C. Saline and distilled water were administered to the NC groups. SJP was administered at various doses including at 0.5 (SL), 5 (SM), and 50 mg/kg (SH). All data are presented as the mean ± standard deviation (<span class="html-italic">n</span> = 3); the different letters (a–d, A–D, I–IV) indicate statistical significance (<span class="html-italic">p</span> &lt; 0.05). Significant differences were evaluated using the one-way analysis of variance followed by Duncan’s test for multiple comparisons. NC, negative control; SL, SJP-low; SM, SJP-medium; SH, SJP-high.</p>
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<p>Inhibitory effects of SJP on Colon26-M3.1-caused lung cancer in BALB/c mice. (<b>a</b>) Intravenous administration. (<b>b</b>) Oral administration. Lung-cancer-bearing mice model induced by the <span class="html-italic">i.v.</span> inoculation of Colon26-M3.1 carcinoma. Saline and distilled water were administered to the NC group. Krestin (50 mg/kg), a known reference drug isolated from <span class="html-italic">Coriolus versicolor</span>, was used in the PC group. SJP was intravenously and orally administered at various doses including at 0.5 (SL), 5 (SM), and 50 mg/kg (SH), followed by <span class="html-italic">i.v.</span> inoculation with Colon26-M3.1 carcinoma. All data are presented as the mean ± standard deviation (<span class="html-italic">n</span> = 8); the different letters (a–d) indicate statistical significance (<span class="html-italic">p</span> &lt; 0.05). Significant differences were evaluated using the one-way analysis of variance followed by Duncan’s test for multiple comparisons. NC, negative control; PC, positive control; SL, SJP-low; SM, SJP-medium; SH, SJP-high.</p>
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<p>Cancer inhibitory effects of SJP on lung cancer in BALB/c mice with impaired NK cell function. Lung-cancer-bearing mice model induced by the <span class="html-italic">i.v.</span> inoculation of Colon26-M3.1 carcinoma. Saline was administered to the NC group. SJP was intravenously administered at 5 mg/kg, followed by <span class="html-italic">i.v.</span> inoculation with Colon26-M3.1 carcinoma. The rabbit anti-asialo-GM1 serum was intravenously injected into the mice, two days before inoculation with Colon26-M3.1 carcinoma, to deplete NK cell function. All data are presented as the mean ± standard deviation (<span class="html-italic">n</span> = 8); the different letters (a–d) indicate statistical significance (<span class="html-italic">p</span> &lt; 0.05). Significant differences were evaluated using the one-way analysis of variance followed by Duncan’s test for multiple comparisons. NC, negative control; SO, SJP-only; AO, anti-asialo-GM1-only; AS, anti-asialo-GM1-SJP.</p>
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<p>Molecular weight of polysaccharide from <span class="html-italic">S. japonica</span> on RID-HPLC. (<b>a</b>) SJP. (<b>b</b>) SJP-CS. (<b>c</b>) SJP-CP. Elution pattern of three polysaccharide fractions on RID-HPLC equipped with Superdex 75 column, stabilized with 50 mM ammonium formate buffer (pH 5.5).</p>
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<p>Scheme tree to separate polysaccharide from <span class="html-italic">S. japonica</span>.</p>
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<p>Effects of polysaccharide fractions isolated from <span class="html-italic">S. japonica</span> on cytokine secretion of murine peritoneal macrophages. (<b>a</b>) IL-6, (<b>b</b>) IL-12, and (<b>c</b>) TNF-α concentration of culture supernatant. The medium and LPS (1 μg/mL) represent the NC and PC, respectively. All data are presented as the mean ± standard deviation (<span class="html-italic">n</span> = 3); the different letters (a–i) indicate statistical significance (<span class="html-italic">p</span> &lt; 0.05). Significant differences were evaluated using the one-way analysis of variance followed by Duncan’s test for multiple comparisons. Among the experimental groups, statistical significance was set at <span class="html-italic">p</span> value &lt; 0.05. NC, negative control; PC, positive control.</p>
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21 pages, 717 KiB  
Review
Fatty Acids in Cnidaria: Distribution and Specific Functions
by Vasily I. Svetashev
Mar. Drugs 2025, 23(1), 37; https://doi.org/10.3390/md23010037 - 13 Jan 2025
Viewed by 305
Abstract
The phylum Cnidaria comprises five main classes—Hydrozoa, Scyphozoa, Hexacorallia, Octocorallia and Cubozoa—that include such widely distributed and well-known animals as hard and soft corals, sea anemones, sea pens, gorgonians, hydroids, and jellyfish. Cnidarians play a very important role in marine ecosystems. The composition [...] Read more.
The phylum Cnidaria comprises five main classes—Hydrozoa, Scyphozoa, Hexacorallia, Octocorallia and Cubozoa—that include such widely distributed and well-known animals as hard and soft corals, sea anemones, sea pens, gorgonians, hydroids, and jellyfish. Cnidarians play a very important role in marine ecosystems. The composition of their fatty acids (FAs) depends on food (plankton and particulate organic matter), symbiotic photosynthetic dinoflagellates and bacteria, and de novo biosynthesis in host tissues. In cnidarian lipids, besides the common FA characteristics of marine organisms, numerous new and rare FAs are also found. All Octocorallia species and some Scyphozoa jellyfish contain polyunsaturated FAs (PUFAs) with 24 and 26 carbon atoms. The coral families can be distinguished by specific FA profiles: the presence of uncommon FAs or high/low levels of common fatty acids. Many of the families have characteristic FAs: Acroporidae are characterized by 18:3n6, eicosapentaenoic acid (EPA) 20:5n3, 22:4n6, and 22:5n3; Pocilloporidae by 20:3n6, 20:4n3, and docosahexaenoic acid 22:6n3 (DHA); and Poritidae by arachidonic acid (AA) and DHA. The species of Faviidae show elevated concentrations of 18:3n6 and 22:5n3 acids. Dendrophylliidae, being azooxanthellate corals, have such dominant acids as EPA and 22:5n3 and a low content of DHA, which is the major PUFA in hermatypic corals. The major and characteristic PUFAs for Milleporidae (class Hydrozoa) are DHA and 22:5n6, though in scleractinian corals, the latter acid is found only in trace amounts. Full article
(This article belongs to the Special Issue Fatty Acids from Marine Organisms, 2nd Edition)
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<p>GC-MS chromatogram of medusa <span class="html-italic">Rhopilema esculentum</span> total lipid FAMEs on SLB-5ms column.</p>
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<p>Multidimensional scale analysis performed using ten FAs selected as marker variables. Filled circles are for Acroporidae; filled squares for Pocilloporidae; filled triangles for Poritidae; open circles for Faviidae; open squares for Dendrophylliidae; filled rhombi for Pectiniidae; and open rhombi for Fungiidae. The plot is redrawn from [<a href="#B48-marinedrugs-23-00037" class="html-bibr">48</a>].</p>
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12 pages, 1562 KiB  
Article
Bioactive Steroids with Structural Diversity from the South China Sea Soft Coral Lobophytum sp. and Sponge Xestospongia sp.
by Lin-Mao Ke, Zi-Ru Zhang, Song-Wei Li, Yan-Bo Zeng, Ming-Zhi Su and Yue-Wei Guo
Mar. Drugs 2025, 23(1), 36; https://doi.org/10.3390/md23010036 - 13 Jan 2025
Viewed by 307
Abstract
A chemical investigation of the soft coral Lobophytum sp. and the sponge Xestospongia sp. from the South China Sea led to the isolation of five steroids, including two new compounds (1 and 4) and one known natural product (3). [...] Read more.
A chemical investigation of the soft coral Lobophytum sp. and the sponge Xestospongia sp. from the South China Sea led to the isolation of five steroids, including two new compounds (1 and 4) and one known natural product (3). Compounds 13 were derived from the soft coral Lobophytum sp., while 4 and 5 were obtained from the sponge Xestospongia sp. The structures of these compounds were determined by extensive spectroscopic analysis, the time-dependent density functional theory–electronic circular dichroism (TDDFT-ECD) calculation method, and comparison with the spectral data previously reported in the literature. The antibacterial and anti-inflammatory activities of isolated compounds were evaluated in vitro. Compounds 13, 4, and 5 exhibited weak antibacterial activity against vancomycin-resistant Enterococcus faecium G1, Streptococcus parauberis KSP28, Photobacterium damselae FP2244, Lactococcus garvieae FP5245, and Pseudomonas aeruginosa ZJ028. Moreover, compound 3 showed significant anti-inflammatory activity by inhibiting lipopolysaccharide (LPS)-induced NO production in RAW 264.7 cells, with an IC50 value of 13.48 μM. Full article
(This article belongs to the Special Issue Bioactive Compounds from Soft Corals and Their Derived Microorganisms)
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<p>Chemical structures of compounds <b>1</b>–<b>7</b>.</p>
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<p><sup>1</sup>H–<sup>1</sup>H COSY, HMBC correlations of <b>1</b> and <b>4</b>, and key NOE correlations of <b>1</b>.</p>
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<p>The determination of absolute configuration of <b>4</b> by the TDDFT-ECD calculation: experimental ECD spectrum of <b>4</b> (black solid line), calculated ECD spectrum of (8<span class="html-italic">S</span>,9<span class="html-italic">S</span>,10<span class="html-italic">R</span>,13<span class="html-italic">R</span>,14<span class="html-italic">S</span>,17<span class="html-italic">R</span>,20<span class="html-italic">R</span>)-<b>4</b> (red dashed line), and mirrored curve of calculated ECD (blue dashed line).</p>
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<p>Cell viability and anti-inflammatory activity results. (<b>A</b>) Cell viabilities of RAW 264.7 cells treated with isolated compounds for 24 h. (<b>B</b>) NO production of RAW 264.7 cells which were pre-treated with <b>3</b> or dexamethasone for 1 h, and then stimulated by LPS for 24 h. <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 and <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 vs. untreated controls; *** <span class="html-italic">p</span> &lt; 0.001 vs. LPS-treated cells.</p>
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20 pages, 679 KiB  
Article
Antioxidant and Anti-Obesity Properties of Acidic and Alkaline Seaweed Extracts Adjusted to Different pH Levels
by Sakhi Ghelichi, Mona Hajfathalian, Sara Falcione and Charlotte Jacobsen
Mar. Drugs 2025, 23(1), 35; https://doi.org/10.3390/md23010035 - 12 Jan 2025
Viewed by 638
Abstract
This research examined antioxidant and anti-obesity effects of Palmaria palmata extracts obtained through acidic or alkaline treatments and subsequent pH adjustments. After two rounds of acidic or alkaline extraction, the extracts were separated from biomass and adjusted to different pH values: for acidic [...] Read more.
This research examined antioxidant and anti-obesity effects of Palmaria palmata extracts obtained through acidic or alkaline treatments and subsequent pH adjustments. After two rounds of acidic or alkaline extraction, the extracts were separated from biomass and adjusted to different pH values: for acidic extracts, pH 3 (no adjustment), pH 6, pH 9, and pH 12; for alkaline extracts, pH 12 (no adjustment), pH 9, pH 6, and pH 3. The findings revealed that extraction medium as well as subsequent pH adjustments significantly influenced composition of the extracts in terms of protein content and recovery, amino acids, and phenolic compounds (p < 0.05). Acidic conditions produced extracts with potent radical scavenging, especially at pH 6 (IC50 = 0.30 ± 0.04 mg.mL−1), while alkaline conditions favored metal chelating, with the highest Fe2+ chelation at pH 12 (IC50 = 0.65 ± 0.03 mg.mL−1). Moreover, extracts showed inhibitory activities against porcine pancreatic lipase and α-amylase, with the acidic extract at pH 9 showing the best anti-obesity properties (IC50 = 5.38 ± 0.34 mg.mL−1 for lipase and IC50 = 5.79 ± 0.30 mg.mL−1 for α-amylase). However, the highest α-amylase activity was in the alkaline extract at pH 12 (IC50 = 3.05 ± 0.66 mg.mL−1). In conclusion, adjusting the pH of seaweed extracts notably influences their bioactive properties, likely due to changes in the reactivity and interactions of bioactive compounds such as peptides, carbohydrates, and polyphenols. Full article
(This article belongs to the Special Issue The Bioactive Potential of Marine-Derived Peptides and Proteins)
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<p>Degree of hydrolysis (DH) of <span class="html-italic">P. palmata</span> extracts after acidic and alkaline extractions and subsequent pH adjustments. Data are expressed as mean ± standard deviation (<span class="html-italic">n</span> = 16). Different letters denote significant differences among the treatments in terms of DH (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Total phenolic content (TPC) of <span class="html-italic">P. palmata</span> extracts after acidic and alkaline extractions and subsequent pH adjustments. Data are expressed as mean ± standard deviation (<span class="html-italic">n</span> = 6). Different letters denote significant differences among the treatments in terms of TPC (<span class="html-italic">p</span> &lt; 0.05).</p>
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46 pages, 15366 KiB  
Review
Investigating Past, Present, and Future Trends on Interface Between Marine and Medical Research and Development: A Bibliometric Review
by Mehdi Zamani, Tetyana Melnychuk, Anton Eisenhauer, Ralph Gäbler and Carsten Schultz
Mar. Drugs 2025, 23(1), 34; https://doi.org/10.3390/md23010034 - 10 Jan 2025
Viewed by 526
Abstract
The convergence of marine sciences and medical studies has the potential for substantial advances in healthcare. This study uses bibliometric and topic modeling studies to map the progression of research themes from 2000 to 2023, with an emphasis on the interdisciplinary subject of [...] Read more.
The convergence of marine sciences and medical studies has the potential for substantial advances in healthcare. This study uses bibliometric and topic modeling studies to map the progression of research themes from 2000 to 2023, with an emphasis on the interdisciplinary subject of marine and medical sciences. Building on the global publication output at the interface between marine and medical sciences and using the Hierarchical Dirichlet Process, we discovered dominating research topics during three periods, emphasizing shifts in research focus and development trends. Our data show a significant rise in publication output, indicating a growing interest in using marine bioresources for medical applications. The paper identifies two main areas of active research, “natural product biochemistry” and “trace substance and genetics”, both with great therapeutic potential. We used social network analysis to map the collaborative networks and identify the prominent scholars and institutions driving this research and development progress. Our study indicates important paths for research policy and R&D management operating at the crossroads of healthcare innovation and marine sciences. It also underscores the significance of quantitative foresight methods and interdisciplinary teams in identifying and interpreting future scientific convergences and breakthroughs. Full article
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<p>Research stages.</p>
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<p>Number of publications per year.</p>
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<p>Hierarchical Dirichlet Process model 2000–2007.</p>
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<p>Hierarchical Dirichlet Process model 2008–2015.</p>
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<p>Hierarchical Dirichlet Process model 2016–2023.</p>
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<p>Topic Trend: Infection and Immunity (2000–2007) to Infectious Disease and Epidemiology (2008–2015).</p>
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<p>Topic Trend: Diet and Food Consumption (2000–2007) to Dietary Impact on Health (2008–2015).</p>
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<p>Topic trend, status, and prediction using S-curve-Exercise Physiology and Hypoxia (2000–2007) to Physical Training and Performance (2008–2015) to Pediatric Exercise and Health (2016–2023).</p>
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<p>Topic trend, status, and prediction using S-curve-Exercise Physiology and Hypoxia (2000–2007) to Physical Training and Performance (2008–2015) to Pediatric Exercise and Health (2016–2023).</p>
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<p>Topic trend, status, and prediction using S-curve-Neuronal Receptor and Protein Research (2000–2007), to Genetics and Molecular Biology (2008–2015), and then to Genetic Expression in Health and Disease (2016–2023).</p>
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<p>Topic trend, status, and prediction using S-curve-Gene Transfer and Aquatic Bacteria (2000–2007), to Aquatic Ecology and Conservation (2008–2015), and then to Marine Microbiology and Biofilm Formation (2016–2023).</p>
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<p>Topic trend, status, and prediction using S-curve-Gene Transfer and Aquatic Bacteria (2000–2007), to Aquatic Ecology and Conservation (2008–2015), and then to Marine Microbiology and Biofilm Formation (2016–2023).</p>
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<p>Topic trend, status, and prediction using S-curve-Heavy Metal Toxicology (2000–2007), to Marine Pollution and Metal Toxicology (2008–2015), and then to Microplastic Contamination and Ecotoxicology (2016–2023).</p>
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<p>Topic trend, status, Prediction-Cancer Cell Research (2000–2007), to Cancer Biology and Therapeutics (2008–2015), and then to Cancer Research and Cellular Mechanisms (2016–2023).</p>
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<p>Topic trend, status, Prediction-Cancer Cell Research (2000–2007), to Cancer Biology and Therapeutics (2008–2015), and then to Cancer Research and Cellular Mechanisms (2016–2023).</p>
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<p>Topic trend, status, and prediction using S-curve-Natural Product Biochemistry (2000–2007), to Natural Products and Bioactive Compounds (2008–2015), and then to Bioactive Natural Compounds (2016–2023).</p>
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<p>Co-country network based on degree centrality.</p>
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<p>Co-organization network based on degree centrality.</p>
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<p>Co-author network based on degree centrality.</p>
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30 pages, 6831 KiB  
Review
Recent Advances in Natural Products Derived from Marine Echinoderms and Endophytic Microbes: Chemical Insights and Therapeutic Potential
by Shuangyu Li, Yan Xiao, Qiang Li, Mingzhi Su, Yuewei Guo and Xin Jin
Mar. Drugs 2025, 23(1), 33; https://doi.org/10.3390/md23010033 - 10 Jan 2025
Viewed by 560
Abstract
Echinoderms, a diverse group of marine invertebrates including starfish, sea urchins, and sea cucumbers, have been recognized as prolific sources of structurally diverse natural products. In the past five years, remarkable progress has been made in the isolation, structural elucidation, and pharmacological assessment [...] Read more.
Echinoderms, a diverse group of marine invertebrates including starfish, sea urchins, and sea cucumbers, have been recognized as prolific sources of structurally diverse natural products. In the past five years, remarkable progress has been made in the isolation, structural elucidation, and pharmacological assessment of these bioactive compounds. These metabolites, including polysaccharides, triterpenoids, steroids, and peptides, demonstrate potent bioactivities such as anticancer, anti-inflammatory, antiviral, and antimicrobial effects, providing valuable insights and scaffolds for drug discovery. This review highlights the structural diversity and biological activities of natural products derived from echinoderms over the last five years, with a particular focus on their structure–activity relationships and therapeutic potential. It also outlines the prospects and challenges for future research, aiming to stimulate further exploration in marine drug discovery. Full article
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<p>The structure of gymnochrome G (<b>1</b>) and strychnine (<b>2</b>).</p>
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<p>The structure of compound <b>3</b>.</p>
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<p>The structure of 6-BHP.</p>
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<p>The structure of penicilloneines A (<b>5</b>) and B (<b>6</b>).</p>
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<p>The structure of catalindoles A–C (<b>7</b>–<b>9</b>).</p>
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<p>The structure of coloquadranoside A (<b>10</b>).</p>
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<p>The structure of quadrangularisoside A (<b>11</b>), quadrangularisoside A<sub>1</sub> (<b>12</b>), quadrangularisoside B (<b>13</b>), quadrangularisoside B1 (<b>14</b>), quadrangularisoside B2 (<b>15</b>), quadrangularisoside C (<b>16</b>), quadrangularisoside C1 (<b>17</b>), quadrangularisoside D (<b>18</b>), quadrangularisoside D1 (<b>19</b>), quadrangularisoside D2 (<b>20</b>), quadrangularisoside D3 (<b>21</b>), quadrangularisoside D4 (<b>22</b>), and quadrangularisoside E (<b>23</b>).</p>
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<p>The structure of chitonoidosides A (<b>24</b>), A<sub>1</sub> (<b>25</b>), B (<b>26</b>), C (<b>27</b>), D (<b>28</b>), E (<b>29</b>), E<sub>1</sub> (<b>30</b>), F (<b>31</b>), G (<b>32</b>), H (<b>33</b>), I (<b>34</b>), J (<b>35</b>), K (<b>36</b>), K<sub>1</sub> (<b>37</b>), and L (<b>38</b>).</p>
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<p>The structure of chilensosides A (<b>39</b>), A<sub>1</sub> (<b>40</b>), B (<b>41</b>), C (<b>42</b>), D (<b>43</b>), E (<b>44</b>), F (<b>45</b>), and G (<b>46</b>).</p>
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<p>The structure of triterpene glycosides: djakonoviosides A (<b>47</b>), A<sub>1</sub> (<b>48</b>), A<sub>2</sub> (<b>49</b>), B<sub>1</sub> (<b>50</b>), B<sub>2</sub> (<b>51</b>), B<sub>3</sub> (<b>52</b>), B<sub>4</sub> (<b>53</b>), C<sub>1</sub> (<b>54</b>), D<sub>1</sub> (<b>55</b>), E<sub>1</sub> (<b>56</b>), and F<sub>1</sub> (<b>57</b>).</p>
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<p>The structure of peronioside A (<b>58</b>).</p>
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<p>The structure of triterpene glycoside echinoside B 12-O-methyl ether (<b>59</b>).</p>
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<p>The structure of triterpene glycosides: desholothurin B (<b>60</b>) and 12-epi-desholothurin B (<b>61</b>).</p>
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<p>The structure of kurilosides A<sub>1</sub> (<b>62</b>), A<sub>2</sub> (<b>63</b>), A<sub>3</sub> (<b>64</b>), C<sub>1</sub> (<b>65</b>), D (<b>66</b>), D<sub>1</sub> (<b>67</b>), E (<b>68</b>), F (<b>69</b>), G (<b>70</b>), H (<b>71</b>), I (<b>72</b>), I<sub>1</sub> (<b>73</b>), J (<b>74</b>), K (<b>75</b>), and K<sub>1</sub> (<b>76</b>).</p>
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<p>The structure of pacificusosides A–Q: A (<b>77</b>), B (<b>78</b>), C (<b>79</b>), D (<b>80</b>), E (<b>81</b>), F (<b>82</b>), G (<b>83</b>), H (<b>84</b>), I (<b>85</b>), J (<b>86</b>), K (<b>87</b>), L (<b>88</b>), M (<b>89</b>), N (<b>90</b>), O (<b>91</b>), P (<b>92</b>), and Q (<b>93</b>).</p>
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<p>The structure of bivittoside E (<b>94</b>).</p>
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<p>The structure of apostichoposide A (<b>95</b>) and apostichoposide B (<b>96</b>).</p>
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<p>The structures of compounds <b>97</b> and <b>98</b>.</p>
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<p>The structure of microdiscusoside A (<b>99</b>) and microdiscusol G (<b>100</b>).</p>
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<p>The structures of compounds <b>101</b>–<b>104</b>.</p>
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<p>The structure of spiculiferosides A-D (<b>105</b>–<b>108</b>).</p>
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<p>The structure of compounds <b>109</b>–<b>112</b>.</p>
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<p>The structure of compounds <b>113</b>–<b>116</b>.</p>
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<p>The structure of compounds <b>117</b>–<b>120</b>.</p>
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<p>The structure of comatulins A−E (<b>121</b>–<b>125</b>).</p>
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<p>The structure of delicapyrons A-E (<b>126</b>–<b>130</b>).</p>
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<p>The structure of salmachroman (<b>131</b>).</p>
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<p>The structure of compound <b>132</b>.</p>
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<p>The structure of sajaroketides A (<b>133</b>) and B (<b>134</b>).</p>
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<p>The structure of compounds <b>135</b>–<b>139</b>.</p>
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<p>The structure of compounds <b>140</b>–<b>142</b>.</p>
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<p>The structure of spiniferosides A-C (<b>143</b>–<b>145</b>).</p>
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<p>The structure of salmacembrane A (<b>146</b>) and B (<b>147</b>).</p>
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<p>The structure of aspergillolide (<b>148</b>).</p>
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<p>The structure of holospiniferoside (<b>149</b>).</p>
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<p>The structure of O-7 (<b>150</b>) and O-8 (<b>151</b>).</p>
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<p>The structure of compounds <b>152</b>–<b>157</b>.</p>
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<p>The structure of herrmananes A and B (<b>158</b> and <b>159</b>).</p>
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<p>The structure of compound <b>160</b>.</p>
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21 pages, 4921 KiB  
Article
Preclinical Efficacy and Proteomic Prediction of Molecular Targets for s-cal14.1b and s-cal14.2b Conotoxins with Antitumor Capacity in Xenografts of Malignant Pleural Mesothelioma
by Angélica Luna-Nophal, Fernando Díaz-Castillo, Vanessa Izquierdo-Sánchez, Jesús B. Velázquez-Fernández, Mario Orozco-Morales, Luis Lara-Mejía, Johana Bernáldez-Sarabia, Noemí Sánchez-Campos, Oscar Arrieta, José Díaz-Chávez, Jorge-Ismael Castañeda-Sánchez, Alexei-Fedorovish Licea-Navarro and Saé Muñiz-Hernández
Mar. Drugs 2025, 23(1), 32; https://doi.org/10.3390/md23010032 - 10 Jan 2025
Viewed by 424
Abstract
Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some [...] Read more.
Malignant pleural mesothelioma (MPM) is a rare neoplasm with increasing incidence and mortality rates. Although recent advances have improved the overall prognosis, they have not had an important impact on survival of patients with MPM, such that more effective treatments are needed. Some species of marine snails have been demonstrated to be potential sources of novel anticancer molecules. This study analyzed the anticancer effects in vitro and in vivo of two peptides found in C. californicus. The effects of s-cal14.1b and s-cal14.2b on cell proliferation, apoptosis, and cytotoxicity were evaluated in 2D and 3D cultures of MPM-derived cells. Proteomics analysis of 3D cultures treated with conotoxins was performed to examine changes in expression or abundance. And the therapeutic effects of both conotoxins were evaluated in MPM mouse xenografts. s-cal14.1b and s-cal14.2b induced apoptosis and cytotoxicity in 2D and 3D cultures. However, only s-cal14.1b modified spheroid growth. Approximately 600 proteins exhibited important differential expression, which was more heterogeneous in H2452 vs MSTO-211H spheroids. The in silico protein functional analysis showed modifications in the biological pathways associated with carcinogenesis. CAPN1, LIMA1, ANXA6, HUWE1, PARP1 or PARP4 proteins could be potential cell targets for conotoxins and serve as biomarkers in MPM. Finally, we found that both conotoxins reduced the tumor mass in MPM xenografts; s-cal14.1b reached statistical significance. Based on these results, s-cal14.1b and s-cal14.2b conotoxins could be potential therapeutic drugs for MPM neoplasms with no apparent side effects on normal cells. Full article
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<p>(<b>A</b>) Percentages of proliferation obtained at 24 h and 48 h post-exposition with s-cal14.1b and s-cal12.2b toxin in monolayers cultures. * The point where <span class="html-italic">p</span> = 0.05, compared the treated vs untreated monolayer. (<b>B</b>) At the top are present plots representative of apoptosis acquisition and at the bottom are present apoptosis percentage graphs. MRC-5 cell lines do not have a statistically significant induction of apoptosis. Percentage of apoptosis induced in H2452 and MSTO-211H cell lines reaches a statistical significance. * Statistical significance <span class="html-italic">p</span> ≤ 0.05.</p>
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<p>Final volume (mm<sup>3</sup>) of spheroids during formation and growth period; arrows indicate the day in which conotoxins were added to culture. * Statistical difference vs control cultures unexposed; <span class="html-italic">p</span> ≤ 0.05.</p>
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<p>The spheroid morphology during formation and growth was monitored for a long time. * The day conotoxins were added to culture. Panels titled PC correspond to phase contrast and FL to fluorescent mark (green) of cytotoxic effects; all images were taken under the same epifluorescence microscopy parameters. Barr = 100 μm.</p>
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<p>Heat maps representing the differential expression according to experimental condition; control refers to proteins in untreated 3D culture (they were previously compared to 2D culture). All treatments’ expressions were compared to the corresponding 3D control. The expression value rang is indicated by color, green for upregulated and red for downregulated.</p>
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<p>Biological process most significant expressed by 3D cultures according to the experimental condition. Proteins are grouped according to their participation in several processes. F and G, after the toxin’s name, represent the formation or growth period, respectively.</p>
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<p>Interaction between proteins in MSTO-211H or H2452 3D cultures. Red squares indicate downregulated proteins and green circles upregulated ones. Interactions between proteins are indicate by black lines. The relationship was generated by Cytoscape software.</p>
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<p>Tumor growth in xenograft model was inhibited by s-cal14.1b; volume is presented as mean ± standard deviation, the follow up was seven weeks. s-cal14.1b showed statistical difference with respect at untreated group mice (blue vs. black line). Right panel, representative images of tumor mass, after sacrifice of the mice. Barr = 15 mm.</p>
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14 pages, 2574 KiB  
Article
Protective Effects of Chitosan Oligosaccharide Against Lipopolysaccharide-Induced Inflammatory Response and Oxidative Stress in Bovine Mammary Epithelial Cells
by Ziwei Lin, Yanlong Zhou, Ruiwen Chen, Qiuyan Tao, Qiwen Lu, Qianchao Xu, Haibin Yu, Ping Jiang and Zhihui Zhao
Mar. Drugs 2025, 23(1), 31; https://doi.org/10.3390/md23010031 - 9 Jan 2025
Viewed by 325
Abstract
Chitosan oligosaccharide (COS) is receiving increasing attention as a feed additive in animal production. COS has a variety of biological functions, including anti-inflammatory and antioxidant activities. Mastitis is a major disease in dairy cows that has a significant impact on animal welfare and [...] Read more.
Chitosan oligosaccharide (COS) is receiving increasing attention as a feed additive in animal production. COS has a variety of biological functions, including anti-inflammatory and antioxidant activities. Mastitis is a major disease in dairy cows that has a significant impact on animal welfare and production. Hence, this research aimed to investigate the mechanism of COS on the lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in bovine mammary epithelial cells (BMECs). In this study, the results demonstrated that COS protected BMECs from the inflammatory response induced by LPS by restraining the excessive production of toll-like receptor 4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). COS treatment also suppressed excessive reactive oxygen species (ROS) production and restored antioxidant enzyme activity under LPS-induced oxidative stress conditions. Furthermore, the results also demonstrated that COS promote nuclear factor erythroid 2-related factor 2 (Nrf2) expression and inhibit TLR4 levels and p65 and IκBα phosphorylation in BMECs exposed to LPS. In summary, the results demonstrate that the protective mechanism of COS on the LPS-induced inflammatory response and oxidative stress depend on the TLR4/nuclear factor-κB (NF-κB) and Nrf2 signaling pathways, indicating that COS could serve as natural protective agents for alleviating BMECs in mastitis. Full article
(This article belongs to the Special Issue Marine Natural Products and Signaling Pathways, 2nd Edition)
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<p>Effect of COS and LPS on BMEC viability. (<b>A</b>) Viability of BMECs treated with 150 μg/mL COS for 36 h. (<b>B</b>) Viability of BMECs pretreated with 150 μg/mL COS for 12 h and co-treated with 10 μg/mL LPS for an additional 24 h. Data are presented as the mean ± standard deviation (SD) (<span class="html-italic">n</span> = 3). ** <span class="html-italic">p</span> &lt; 0.01 indicates a statistically significant difference.</p>
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<p>COS alleviated the LPS-induced inflammatory response in BMECs. The mRNA levels of (<b>A</b>) <span class="html-italic">TLR4</span>, (<b>B</b>) <span class="html-italic">TNF-α</span>, (<b>C</b>) <span class="html-italic">IL-1β</span>, and (<b>D</b>) <span class="html-italic">IL-6</span> were assessed using real-time quantitative PCR (RT-qPCR). The protein expression of (<b>E</b>) TLR4, (<b>F</b>) TNF-α, (<b>G</b>) IL-1β, and (<b>H</b>) IL-6 was tested using ELISAs. Data are presented as the mean ± SD (<span class="html-italic">n</span> = 3). Groups with different superscript letters were considered statistically different (<span class="html-italic">p</span> &lt; 0.05)).</p>
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<p>COS mitigated LPS-induced oxidative stress in BMECs. (<b>A</b>) Effects of COS on ROS fluorescence intensities in LPS-induced BMECs. Fluorescence microscopic images showing ROS production. (<b>B</b>) The fluorescence intensities were analyzed using Image J. (<b>C</b>,<b>D</b>) SOD and CAT activities. (<b>E</b>) <span class="html-italic">Nrf2</span> mRNA expression as assessed with RT-qPCR. Scale bar = 100 μm. Data are presented as the mean ± SD (<span class="html-italic">n</span> = 3). Groups with different superscript letters are statistically different (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>COS alleviated oxidative stress and inflammatory response induced by LPS by regulating Nrf2 and the TLR4/NF-κB signaling pathway. (<b>A</b>) Western blot (WB) images of Nrf2. (<b>B</b>) Quantification analysis of Nrf2 expression. (<b>C</b>) WB images of TLR4, p-IκBα, IκBα, p-p65, and p65. The quantification analysis of (<b>D</b>) TLR4, (<b>E</b>) p-IκBα/IκBα, and (<b>F</b>) p-p65/p65 expression. Data are presented as the mean ± SD (<span class="html-italic">n</span> = 3). Groups with different superscript letters are considered statistically different (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>COS alleviated oxidative stress and inflammatory response induced by LPS by regulating Nrf2 and the TLR4/NF-κB signaling pathway. (<b>A</b>) Western blot (WB) images of Nrf2. (<b>B</b>) Quantification analysis of Nrf2 expression. (<b>C</b>) WB images of TLR4, p-IκBα, IκBα, p-p65, and p65. The quantification analysis of (<b>D</b>) TLR4, (<b>E</b>) p-IκBα/IκBα, and (<b>F</b>) p-p65/p65 expression. Data are presented as the mean ± SD (<span class="html-italic">n</span> = 3). Groups with different superscript letters are considered statistically different (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Protective mechanisms of COS in LPS-induced BMECs (image generated using Figdraw).</p>
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26 pages, 4334 KiB  
Article
Biochemical Composition and Seasonal Variations of the Madagascar Algae Eucheuma denticulatum (Solieriaceae, Rhodophyta)
by Elando Fréda Zamanileha, Anne-Sophie Burlot, Thomas Latire, Christel Marty, Philippe Douzenel, Laurent Vandanjon, Nathalie Bourgougnon, Pierre Ravelonandro and Gilles Bedoux
Mar. Drugs 2025, 23(1), 30; https://doi.org/10.3390/md23010030 - 9 Jan 2025
Viewed by 451
Abstract
Although the density and diversity of seaweeds in Madagascar is particularly high, these resources are underexploited and they are not part of the local population’s eating habits. No study has been carried out on the nutritional properties and seasonal variation of Eucheuma species [...] Read more.
Although the density and diversity of seaweeds in Madagascar is particularly high, these resources are underexploited and they are not part of the local population’s eating habits. No study has been carried out on the nutritional properties and seasonal variation of Eucheuma species harvested in Madagascar. In this study, Eucheuma denticulatum was harvested monthly over two years (2021 and 2022) on the northeast coast of Madagascar (Sainte Marie Island). The compositional analysis revealed prominent sugars and minerals up to 41.0 and 39.5% dw, respectively. E. denticulatum showed slight variability over the seasons in the macroelements and oligoelements (Ca, K, Na, Mg, Fe, Mn) ranging from 22.8 ± 0.2 to 25.3 ± 0.1% dw in 2021 and 22.1 ± 0.3 to 26.5 ± 0.3% dw in 2022. Total amino acids varied from 2.3 ± 0.6 to 2.5 ± 0.6% dw during the two years. Seaweed extracts showed antioxidant activity by the in vitro method ranging from 2026 ± 2 to 2998 ± 4 μg.mL−1 in 2021, and from 1904 ± 2 to 2876 ± 4 μg.mL−1 in 2022. Finally, the principal component analysis (PCA) showed a correlation between protein content and environmental parameters. The nutritional characteristics therefore confirmed that E. denticulatum could potentially be used as a nutritious and functional food and could be incorporated in the diet of local populations. Full article
(This article belongs to the Special Issue Bioactive Polysaccharides from Seaweeds)
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Graphical abstract

Graphical abstract
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<p>Follow-up of variations in environmental and abiotic factors through variations in temperature, sunshine, wind speed and precipitation (<b>a</b>) and variations in seawater salts (salinity, nitrate, ammonium, dissolved oxygen and phosphate) (<b>b</b>), years 2021 and 2022 (summer season October–January and winter season May–September).</p>
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<p>Extract of FTIR spectra of standard iota carrageenan and <span class="html-italic">Eucheuma denticulatum</span> polysaccharides collected in January 2022.</p>
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<p>Mineral composition in <span class="html-italic">Eucheuma denticulatum</span> from Madagascar years 2021 and 2022 in % dw: (<b>a</b>) macroelement composition and (<b>b</b>) oligoelements composition.</p>
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<p>Amino acid profile of <span class="html-italic">Eucheuma denticulatum</span>, expressed in (% AA) dry matter of total amino acids detected by LC.</p>
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<p>Principal component analysis (PCA) of the influence of seasonal variations of <span class="html-italic">E. denticulatum</span> on these abiotic and environmental factors and biochemical compositions during the year 2021–2022.</p>
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16 pages, 8075 KiB  
Article
Structure of a Sulfated Capsular Polysaccharide from the Marine Bacterium Cobetia marina KMM 1449 and a Genomic Insight into Its Biosynthesis
by Maxim S. Kokoulin, Yulia V. Savicheva, Alina P. Filshtein, Ludmila A. Romanenko and Marina P. Isaeva
Mar. Drugs 2025, 23(1), 29; https://doi.org/10.3390/md23010029 - 8 Jan 2025
Viewed by 438
Abstract
Some marine and extremophilic microorganisms are capable of synthesizing sulfated polysaccharides with a unique structure. A number of studies indicate significant biological properties of individual sulfated polysaccharides, such as antiproliferative activity, which makes them a promising area for further research. In this study, [...] Read more.
Some marine and extremophilic microorganisms are capable of synthesizing sulfated polysaccharides with a unique structure. A number of studies indicate significant biological properties of individual sulfated polysaccharides, such as antiproliferative activity, which makes them a promising area for further research. In this study, the capsular polysaccharide (CPS) was obtained from the bacterium Cobetia marina KMM 1449, isolated from a marine sediment sample collected along the shore of the Sea of Japan. The CPS was isolated by saline solution, purified by a series of chromatographic procedures, and studied by chemical methods along with 1D and 2D 1H and 13C NMR spectroscopy. The following new structure of the CPS from C. marina KMM 1449 was established and consisted of sulfated and simultaneously phosphorylated disaccharide repeating units: →4)-α-L-Rhap2S-(1→3)-β-D-Manp6PGro-(1→. To elucidate the genetic basis of the CPS biosynthesis, the whole genomic sequence of C. marina KMM 1449 was obtained. The CPS biosynthetic gene cluster (BGC) of about 70 genes composes four regions encoding nucleotide sugar biosynthesis (dTDP-Rha and GDP-Man), assembly (GTs genes), translocation (ABC transporter genes), sulfation (PAPS biosynthesis and sulfotransferase genes) and lipid carrier biosynthesis (wcb operon). Comparative analysis of the CPS BGCs from available Cobetia genomes showed the presence of KMM 1449-like CPS BGC among strains of all three Cobetia species. The study of new natural sulfated polysaccharides, as well as the elucidation of the pathways of their biosynthesis, provides the basis for the development of potential anticancer drugs. Full article
(This article belongs to the Special Issue Exopolysaccharide Isolated from Marine Microorganisms)
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Figure 1
<p><sup>1</sup>H NMR spectrum (<b>A</b>) and <sup>13</sup>C NMR spectrum (<b>B</b>) of the CPS from <span class="html-italic">C. marina</span> KMM 1449. Numerals refer to carbons and protons in sugar residues denoted by capital letters, as described in <a href="#marinedrugs-23-00029-t001" class="html-table">Table 1</a>.</p>
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<p><sup>1</sup>H NMR spectrum (<b>A</b>) and <sup>13</sup>C NMR spectrum (<b>B</b>) of the dPCPS from <span class="html-italic">C. marina</span> KMM 1449. Numerals refer to carbons and protons in sugar residues denoted by capital letters, as described in <a href="#marinedrugs-23-00029-t001" class="html-table">Table 1</a>.</p>
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<p><sup>1</sup>H, <sup>13</sup>C HSQC spectrum of the dPCPS from <span class="html-italic">C. marina</span> KMM 1449. Numerals refer to carbons and protons in sugar residues denoted by capital letters, as described in <a href="#marinedrugs-23-00029-t001" class="html-table">Table 1</a>.</p>
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<p>Fragments of the <sup>1</sup>H, <sup>1</sup>H ROESY spectrum (<b>A</b>) and <sup>1</sup>H, <sup>13</sup>C HMBC spectrum (<b>B</b>,<b>C</b>) of the dPCPS from <span class="html-italic">C. marina</span> KMM 1449. Numerals refer to carbons and protons in sugar residues denoted by capital letters, as described in <a href="#marinedrugs-23-00029-t001" class="html-table">Table 1</a>.</p>
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<p>Genomic tree of <span class="html-italic">Cobetia</span> strains inferred with FastME 2.1.6.1 [<a href="#B19-marinedrugs-23-00029" class="html-bibr">19</a>] based on GBDP distances (formula d5). GBDP pseudo-bootstrap support values are shown &gt;50% from 100 replications. The average branch support was 83.5%. The tree was rooted at the midpoint. Strains with KMM 1449-like CPS gene cluster organization are marked with a red diamond, and strains with known polysaccharide structures are marked with a blue circle. KMM 1449 is marked in bold.</p>
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<p>Chromosome location (<b>a</b>) and gene cluster organization (<b>b</b>) for the KMM 1449 CPS biosynthesis. Visualization was performed on the Proksee server [<a href="#B24-marinedrugs-23-00029" class="html-bibr">24</a>]. The scale is shown in megabases (Mbp) for chromosomes and in kilobases (Kbp) for gene clusters. A gene for UDP-D-Glc biosynthesis is shown in red on chromosomes.</p>
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<p>A scheme of metabolic pathways for the biosynthesis of activated nucleotide sugars for <span class="html-italic">Cobetia</span> KMM 1449 CPS obtained from genomic sequence data. The EC numbers identify the corresponding enzymes: EC 3.2.1.20 alpha-glucosidase; EC 2.7.1.2 glucokinase; EC 5.3.1.9 glucose-6-phosphate isomerase; EC 5.4.2.2 phosphoglucomutase; EC 2.7.7.9 UTP-glucose-1-phosphate uridylyltransferase; EC 2.7.7.24 glucose-1-phosphate thymidylyltransferase; EC 4.2.1.46 dTDP-glucose 4,6-dehydratase; EC 5.1.3.13 dTDP-4-dehydrorhamnose 3,5-epimerase; EC 1.1.1.133 dTDP-4-dehydrorhamnose reductase; EC 1.1.1.67 mannitol 2-dehydrogenase; EC 2.7.1.90 6-phosphofructokinase; EC 2.2.1.1 transketolase; EC 5.3.1.8 mannose-6-phosphate isomerase; EC 5.4.2.8 phosphomannomutase; EC 2.7.7.13 mannose-1-phosphate guanylyltransferase; EC 2.7.1.56 1-phosphofructokinase; EC 2.7.1.17 xylulokinase; EC 5.3.1.5 xylose isomerase; GT, glycosyltransferases; ST, sulfotransferase.</p>
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<p>The comparisons of CPS gene loci between the <span class="html-italic">Cobetia</span> representatives. KMM 1449, <span class="html-italic">C. marina</span>; D5, <span class="html-italic">Cobetia</span> sp.; N-80, <span class="html-italic">C. amphilecti</span>; ena-yuan-GCF_007786215.1, <span class="html-italic">C. crustatorum</span>; MM1IDA2H-1AD, <span class="html-italic">C. marina</span>; cqz5-12, <span class="html-italic">Cobetia</span> sp.; and KMM 3879, <span class="html-italic">C. marina</span>; KMM 3880, <span class="html-italic">C. amphilecti</span>.</p>
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14 pages, 1768 KiB  
Article
Expression Analysis of Heavy-Chain-Only Antibodies in Cloudy Catshark and Japanese Bullhead Shark
by Reo Uemura, Susumu Tanimura, Nao Yamaguchi, Ryuichi Kuroiwa, Gabriel Takashi Andrés Tsutsumi, Toshiaki Fujikawa, Kiyoshi Soyano, Kohsuke Takeda and Yoshimasa Tanaka
Mar. Drugs 2025, 23(1), 28; https://doi.org/10.3390/md23010028 - 8 Jan 2025
Viewed by 452
Abstract
Heavy chain-only antibodies in sharks are called immunoglobulin new antigen receptors (IgNAR), consisting of one variable region (VNAR) and five constant regions (C1-C5). The variable region of IgNAR can be expressed as a monomer composed of a single domain, which has antigen specificity [...] Read more.
Heavy chain-only antibodies in sharks are called immunoglobulin new antigen receptors (IgNAR), consisting of one variable region (VNAR) and five constant regions (C1-C5). The variable region of IgNAR can be expressed as a monomer composed of a single domain, which has antigen specificity and is thus gaining attention as a next-generation antibody drug modality. In this study, we analyzed IgNAR of the cloudy catshark and Japanese bullhead shark, small demersal sharks available in the coastal waters of Japan. By analyzing the IgNAR gene sequence and comparing it with the constant regions of five other known shark species, high homology was observed in the C4 region. Consequently, we expressed the recombinant protein of the C4 domain from the cloudy catshark in E. coli, immunized rats, and produced antibodies. The obtained antiserum and mAbs recognized the C4 recombinant protein of the cloudy catshark, but reacted minimally with the plasma of non-immunized cloudy catsharks and instead reacted with the plasma of Japanese bullhead sharks. The results of this study imply that the protein expression levels of IgNAR in cloudy catsharks may be relatively lower compared to those in Japanese bullhead sharks, however, this interpretation remains to be determined through further studies. Full article
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<p>Expression and purification of the C4 domain (Tora-C4) recombinant protein of the cloudy catshark. (<b>A</b>) The amino acid sequence of the Tora-C4 recombinant protein expressed in <span class="html-italic">E. coli</span>. (<b>B</b>) Purification of the Tora-C4 recombinant protein on gel filtration. The Tora-C4 recombinant protein was expressed as inclusion bodies in <span class="html-italic">E. coli</span>, dissolved, and refolded, followed by purification on anion exchange column chromatography. The fraction containing the Tora-C4 recombinant protein was further purified on gel filtration. (<b>C</b>) Analysis of the purified Tora-C4 recombinant protein by SDS-PAGE. The purified Tora-C4 recombinant protein was resolved by SDS-PAGE, and the gel was stained with CBB.</p>
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<p>Analysis of IgNAR expression patterns by ELISA using anti-Tora-C4 serum. (<b>A</b>) The reactivity of anti-Tora-C4 serum against Tora-C4 recombinant protein and bovine serum albumin (BSA) was analyzed by ELISA. Data are shown as the mean ± S.E.M. (<span class="html-italic">n</span> = 4 samples). *** <span class="html-italic">p</span> &lt; 0.001, Tukey–Kramer’s HSD test, Control serum vs. Tora-C4 antiserum in each serum dilution. ### <span class="html-italic">p</span> &lt; 0.001, Tukey–Kramer’s HSD test, BSA vs. Tora-C4 in each Tora-C4 antiserum dilution. (<b>B</b>) The reactivity of anti-Tora-C4 serum against cloudy catshark plasma was analyzed by ELISA. Data are shown as the mean ± S.E.M. (<span class="html-italic">n</span> = 4 samples). (<b>C</b>) The reactivity of anti-Tora-C4 serum against Japanese bullhead shark plasma was analyzed by ELISA. Data are shown as the mean ± S.E.M. (<span class="html-italic">n</span> = 4 samples). *** <span class="html-italic">p</span> &lt; 0.001, Student’s <span class="html-italic">t</span>-test, Control serum vs. Tora-C4 antiserum in each serum dilution.</p>
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<p>Analysis of IgNAR expression patterns by ELISA using anti-Tora-C4 mAb. (<b>A</b>) The reactivity of anti-Tora-C4 mAb against Tora-C4 recombinant protein was analyzed by ELISA. (<b>B</b>) The reactivity of 12 different anti-Tora-C4 mAbs against cloudy catshark plasma was analyzed by ELISA. Data are shown as the mean ± S.E.M. (<span class="html-italic">n</span> = 4 samples).</p>
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<p>Analysis of IgNAR expression patterns by immunoblotting using anti-Tora-C4 mAb. (<b>A</b>) The reactivity of the culture supernatants (1/20 dilution) from five distinct Tora-C4 hybridoma clones against Tora-C4 recombinant protein was analyzed by immunoblotting. (<b>B</b>) The reactivity of the culture supernatants (1/20 dilution) from five Tora-C4 hybridoma clones against cloudy catshark plasma (10 μg) was determined by immunoblotting. (<b>C</b>) The reactivity of the culture supernatant (undiluted) from the 2D3 hybridoma clone against the plasma (30 μg) from different cloudy catshark individuals and Japanese bullhead shark plasma (30 μg) was determined by immunoblotting. The black arrow indicates a band of approximately 75 kDa, presumed to be Japanese bullhead shark-derived IgNAR.</p>
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36 pages, 4076 KiB  
Review
A Comparative Review of Alternative Fucoidan Extraction Techniques from Seaweed
by Matthew Chadwick, Loïc G. Carvalho, Carlos Vanegas and Simone Dimartino
Mar. Drugs 2025, 23(1), 27; https://doi.org/10.3390/md23010027 - 7 Jan 2025
Viewed by 1157
Abstract
Fucoidan is a sulfated polysaccharide found in brown seaweed. Due to its reported biological activities, including antiviral, antibacterial and anti-inflammatory activities, it has garnered significant attention for potential biomedical applications. However, the direct relationship between fucoidan extracts’ chemical structures and bioactivities is unclear, [...] Read more.
Fucoidan is a sulfated polysaccharide found in brown seaweed. Due to its reported biological activities, including antiviral, antibacterial and anti-inflammatory activities, it has garnered significant attention for potential biomedical applications. However, the direct relationship between fucoidan extracts’ chemical structures and bioactivities is unclear, making it extremely challenging to predict whether an extract will possess a given bioactivity. This relationship is further complicated by a lack of uniformity in the recent literature in terms of the assessment and reporting of extract properties, yield and chemical composition (e.g., sulfate, fucose, uronic acid and monosaccharide contents). These inconsistencies pose significant challenges when directly comparing extraction techniques across studies. This review collected data on extract contents and properties from a selection of available studies. Where information was unavailable directly, efforts were made to extrapolate data. This approach enabled a comprehensive examination of the correlation between extraction techniques and the characteristics of the resulting extracts. A holistic framework is presented for the selection of fucoidan extraction methods, outlining key heuristics to consider when capturing the broader context of a seaweed bioprocess. Future work should focus on developing knowledge within these heuristic categories, such as the creation of technoeconomic models of each extraction process. This framework should allow for a robust extraction selection process that integrates process scale, cost and constraints into decision making. Key quality attributes for biologically active fucoidan are proposed, and areas for future research are identified, such as studies for specific bioactivities aimed at elucidating fucoidan’s mechanism of action. This review also sets out future work required to standardize the reporting of fucoidan extract data. Standardization could positively enhance the quality and depth of data on fucoidan extracts, enabling the relationships between physical, chemical and bioactive properties to be identified. Recommendations on best practices for the production of high-quality fucoidan with desirable yield, characteristics and bioactivity are highlighted. Full article
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<p>Overview of the biological and process factors affecting fucoidan structure.</p>
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<p>Schematic overview of a typical bioprocess for the production of fucoidans from brown seaweed.</p>
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<p>Number of papers published per year that were considered in this review. Enzyme-assisted extraction (EAE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and pressurized liquid extraction (PLE).</p>
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<p>Alluvial diagram showing the taxonomical distribution of seaweed employed in the literature for the various extraction methods: enzyme-assisted extraction (EAE), ultrasound-assisted extraction (UAE), microwave-assisted extraction (MAE) and pressurized liquid extraction (PLE).</p>
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<p>Boxplots of the effect of extraction techniques on fucoidan extract (<b>a</b>) yield, (<b>b</b>) purity, (<b>c</b>) total sugar, (<b>d</b>) fucose, (<b>e</b>) sulfate content, (<b>f</b>) molecular weight, (<b>g</b>) uronic acid content and (<b>h</b>) phenolic content across the different extraction techniques. The shaded region indicates typical values for traditional extraction methods, a line indicates the median and indicates the mean of each data set.</p>
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16 pages, 2308 KiB  
Article
A Comparative Study of the In Vitro Intestinal Permeability of Pinnatoxins and Portimine
by Rachelle Lanceleur, Vincent Hort, Marion Peyrat, Denis Habauzit, Andrew I. Selwood and Valérie Fessard
Mar. Drugs 2025, 23(1), 26; https://doi.org/10.3390/md23010026 - 7 Jan 2025
Viewed by 399
Abstract
The pinnatoxins (PnTXs) and portimines, produced by Vulcanodinium rugosum, have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body [...] Read more.
The pinnatoxins (PnTXs) and portimines, produced by Vulcanodinium rugosum, have been detected in several countries, raising concerns for human health. Although no human poisoning from these toxins has been reported so far, they have been shown to distribute throughout the rodent body after oral administration. Therefore, we investigated the impact of PnTX analogs (PnTX-A, -E, -F, -G, and -H) and portimine (8, 16, and 32 ng/mL) on intestinal barrier integrity and their oral bioavailability using human Caco-2 cell monolayers treated for 2, 6, and 24 h. Our results demonstrated that all of the toxins could impair barrier integrity after 24 h, with differences observed for PnTX-A, -E, and -F, as well as portimine, the most potent of all. While PnTX-A and -E exhibited poor permeability, the other PnTXs were more penetrative, with a Papp > 1.5 × 10−6 cm·s−1. Portimine was the only toxin displaying both a time- and concentration-dependent passage, likely involving a passive diffusion process. The experimental results were compared to predictions obtained by QSAR tools. Although only qualitative, our results suggest that some of these compounds may be more likely to be distributed throughout the body. Further in vivo studies are required to estimate oral bioavailability and potential public health concerns. Full article
(This article belongs to the Special Issue Marine Biotoxins 3.0)
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<p>Structures of the toxins tested in this study and portimine-B.</p>
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<p>Trans-epithelial electrical resistance (TEER) of differentiated Caco-2 cells after incubation with PnTX-A, PnTX-E, PnTX-F, PnTX-G, PnTX-H, and portimine (8, 16, and 32 ng/mL) during 2 h (light grey), 6 h (grey), and 24 h (dark grey) or solvent control (SC, 1.5% MeOH, or 1.5% acetic acid/acetonitrile, dashed line). Results are depicted as mean ± standard deviation of 3 biological replicates (excluding PnTX-G, PnTX-H, and portimine at 24 h, for which only two replicates were available) and are normalized to the solvent control (dashed line). Statistical significance between the solvent control and the treated samples is indicated by * <span class="html-italic">p</span> ≤ 0.05 and **** <span class="html-italic">p</span> ≤ 0.0001.</p>
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<p>Lucifer Yellow fluorescence intensity in the basolateral compartment after incubation with PnTX-A, PnTX-E, PnTX-F, PnTX-G, PnTX-H, and portimine (8, 16, and 32 ng/mL) during 2 h (light grey), 6 h (grey), and 24 h (dark grey) compared to the solvent control (SC, 1.5% MeOH, or 1.5% acetic acid/acetonitrile, dashed line). Results are depicted as mean ± standard deviation of at least three biological replicates (excluding PnTX-G, PnTX-H, and portimine at 24 h, for which only two replicates were available). Statistical significance between the solvent control and the treated samples is indicated by * <span class="html-italic">p</span> ≤ 0.05, ** <span class="html-italic">p</span> ≤0.01, *** <span class="html-italic">p</span>≤ 0.001 and **** <span class="html-italic">p</span> ≤ 0.0001.</p>
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48 pages, 3635 KiB  
Review
Bioactive Angucyclines/Angucyclinones Discovered from 1965 to 2023
by Hai-Shan Liu, Hui-Ru Chen, Shan-Shan Huang, Zi-Hao Li, Chun-Ying Wang and Hua Zhang
Mar. Drugs 2025, 23(1), 25; https://doi.org/10.3390/md23010025 - 5 Jan 2025
Viewed by 491
Abstract
Angucyclines/angucyclinones, a class of polyketides with diverse chemical structures, display various bioactivities including antibacterial or antifungal, anticancer, anti-neuroinflammatory, and anti-α-glucosidase activities. Marine and terrestrial microorganisms have made significant contributions to the discovery of bioactive angucyclines/angucyclinones. This review covers 283 bioactive angucyclines/angucyclinones discovered from [...] Read more.
Angucyclines/angucyclinones, a class of polyketides with diverse chemical structures, display various bioactivities including antibacterial or antifungal, anticancer, anti-neuroinflammatory, and anti-α-glucosidase activities. Marine and terrestrial microorganisms have made significant contributions to the discovery of bioactive angucyclines/angucyclinones. This review covers 283 bioactive angucyclines/angucyclinones discovered from 1965 to 2023, and the emphasis is on the biological origins, chemical structures, and biological activities of these interesting natural products. Full article
(This article belongs to the Special Issue Natural Products Isolated from Marine Sediment)
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Figure 1
<p>PRISMA 2020 flow diagram for systematic reviews.</p>
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<p>Structures of compounds <b>1</b>–<b>35.</b></p>
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<p>Structures of compounds <b>36</b>–<b>61.</b></p>
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<p>Structures of compounds <b>62</b>–<b>93.</b></p>
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<p>Structures of compounds <b>94</b>–<b>106.</b></p>
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<p>Structures of compounds <b>107</b>–<b>142.</b></p>
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<p>Structures of compounds <b>143</b>–<b>160.</b></p>
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<p>Structures of compounds <b>161</b>–<b>195.</b></p>
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<p>Structures of compounds <b>196</b>–<b>216.</b></p>
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<p>Structures of compounds <b>217</b>–<b>241.</b></p>
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<p>Structures of compounds <b>242</b>–<b>283.</b></p>
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<p>Biosynthesis of landomycins.</p>
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<p>(<b>a</b>) Proportion of angucyclines/angucyclinones from different sources. (<b>b</b>) Active types of angucyclines/angucyclinones from different sources. (<b>c</b>) Producer of bioactive angucyclines/angucyclinones. (<b>d</b>) The discovery time of active angucyclines/angucyclinones.</p>
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<p>(<b>a</b>) Proportion of glycosylated angucyclines/angucyclinones. (<b>b</b>) Active types of angucyclines/angucyclinones with different lengths of oligosaccharide chains.</p>
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21 pages, 8475 KiB  
Article
Identification of Novel LCN2 Inhibitors Based on Construction of Pharmacophore Models and Screening of Marine Compound Libraries by Fragment Design
by Ningying Zheng, Xuan Li, Nan Zhou and Lianxiang Luo
Mar. Drugs 2025, 23(1), 24; https://doi.org/10.3390/md23010024 - 5 Jan 2025
Viewed by 547
Abstract
LCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore [...] Read more.
LCN2, a member of the lipocalin family, is associated with various tumors and inflammatory conditions. Despite the availability of known inhibitors, none have been approved for clinical use. In this study, marine compounds were screened for their ability to inhibit LCN2 using pharmacophore models. Six compounds were optimized for protein binding after being docked against the positive control Compound A. Two compounds showed promising results in ADMET screening. Molecular dynamics simulations were utilized to predict binding mechanisms, with Compound 69081_50 identified as a potential LCN2 inhibitor. MM-PBSA analysis revealed key amino acid residues that are involved in interactions, suggesting that Compound 69081_50 could be a candidate for drug development. Full article
(This article belongs to the Special Issue Chemoinformatics for Marine Drug Discovery)
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<p>Hydrophobic group features are represented by blue spheres, aromatic ring features are represented by orange spheres, and hydrogen bond donor features are represented by green spheres. (<b>a</b>) RL_5, RL_7, and RL_9 pharmacophores. (<b>b</b>) Pharmacophore of RL_5. (<b>c</b>) ROC curve of RL_5. (<b>d</b>) Comparative fitness plots of active small molecules of RL_5, RL_7, and RL_9.</p>
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<p>Hydrophobic group features are indicated by blue spheres and hydrogen bond donor features are indicated by green spheres. (<b>a</b>) RL_6, RL_8, and RL_10 pharmacophores. (<b>b</b>) RL_8 pharmacophore. (<b>c</b>) ROC curve of RL_8. (<b>d</b>) Comparative fitness plots of active small molecules of RL_6, RL_8, and RL_10.</p>
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<p>(<b>a</b>) 2D interaction diagram of Compound 44879 with LCN2. The rosy-red part is 2-methylpropan-1-amine. (<b>b</b>) 2D interaction diagram of Compound 46563 with LCN2. The rosy-red portion is 3,6-dimethoxy-2-methyltetrahydro-2H-pyran-4-ol. (<b>c</b>) 2D interaction plot of Compound 50616 with LCN2. The rosy-red part is isopentane. (<b>d</b>) 2D interaction diagram of Compound 50617 with LCN2. (Z)-2-methyl-1-propylguanidine is the rosy-red portion. (<b>e</b>) 2D interaction diagram of Compound 50618 with LCN2. The rosy-red portion is 1,1-dimethyl-3-propylguanidine. (<b>f</b>) 2D interaction diagram of Compound 69081 with LCN2. The rosy-red portion is 3-methoxy-5-methylphenol.</p>
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<p>Hexagonal range distribution of ADME properties of candidate Compounds 44879_4, 69081_38, and 69081_50. (<b>a</b>) Distribution of ADME properties of Compound 44879_4; (<b>b</b>) Distribution of ADME properties of Compound 69081_38; (<b>c</b>) Distribution of ADME properties of Compound 69081_50.</p>
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<p>Results of the molecular dynamics simulations of protein–ligand complexes. (<b>a</b>) RMSD diagram of protein–ligand complex. (<b>b</b>) RMSF diagram of protein–ligand complex. (<b>c</b>) Radius of gyration (Rg) graph for complexes with respect to 100 ns of molecular dynamics. (<b>d</b>) The hydrogen bond of protein with Compound 69081_38. (<b>e</b>) The hydrogen bond of protein with Compound 69081_50. (<b>f</b>) The hydrogen bond of protein with Compound A.</p>
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<p>(<b>a</b>) Three-dimensional binding pattern of Compound 69081_50 to LCN2 protein. Carbon–hydrogen bonds are shown by pale green dashed lines, hydrogen bonds are shown by green dashed lines, alkyl bonds are shown by pink dashed lines, and Pi interactions are shown by magenta dashed lines. (<b>b</b>) The small green molecule is Compound 69081_50, showing the binding of Compound 69081_50 to the LCN2 protein pocket. (<b>c</b>) Schematic of the two-dimensional interaction of Compound 69081_50 with the LCN2 protein.</p>
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<p>Overlapping effects of 10 receptor–ligand complex-based pharmacophore models.</p>
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<p>The 5NKN eutectic with redocked ligand in superposition state. (<b>a</b>) Maestro: superposition state of 5NKN eutectic with redocked ligand (original eutectic ligand in red, redocked ligand in blue) (RMSD: 1.2575 Å). (<b>b</b>) Discovery Studio: superposition state of 5NKN eutectic with redocked ligand (original eutectic ligand in red, redocked ligand in blue) (RMSD: 0.76875 Å).</p>
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15 pages, 6024 KiB  
Article
Identification of Filovirus Entry Inhibitors from Marine Fungus-Derived Indole Alkaloids
by Leah Liu Wang, Javier Seravalli, Brett Eaton, Yi Liu, Michael R. Holbrook, Wen-Jian Lan and Shi-Hua Xiang
Mar. Drugs 2025, 23(1), 23; https://doi.org/10.3390/md23010023 - 3 Jan 2025
Viewed by 734
Abstract
Filoviruses, mainly consisting of the two genera of Ebolavirus and Marburgvirus, are enveloped negative-strand RNA viruses that can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. However, we still do not have effective medicines for treating these [...] Read more.
Filoviruses, mainly consisting of the two genera of Ebolavirus and Marburgvirus, are enveloped negative-strand RNA viruses that can infect humans to cause severe hemorrhagic fevers and outbreaks with high mortality rates. However, we still do not have effective medicines for treating these diseases. To search for effective drugs, we have identified three marine indole alkaloids that exhibit potent activities against filovirus infection. Thus, it is suggested that marine indole alkaloids can be a valuable compound source for filovirus drug screening and development. Since marine indole alkaloids comprise a large diverse group of secondary metabolites, their biological properties would be helpful for pharmaceutical drug development to treat various filovirus infections. Full article
(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 2nd Edition)
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<p>Screening of thirty-one W compounds at 10 µM concentration against pseudotyped filoviruses. EBOV: (<b>A</b>,<b>B</b>): MARV: (<b>C</b>,<b>D</b>). Cells only, TZM-bl cells without compounds as the negative control; Virus only, only viruses without compounds as the positive control.</p>
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<p>Evaluation of compound cytotoxicity in TZM-bl cells using MTT assay. All thirty-one W compounds were applied for the test at 10 µM concentration for the test Cells only, without compounds.</p>
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<p>CC<sub>50</sub> analysis (50% cytotoxicity concentration) of W12, W26 and W27 in TZM-bl cells using MTT assay. The toxicity was evaluated from 2 µM to 32 µM of compound concentrations.</p>
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<p>IC<sub>50</sub> analysis (50% maximal inhibitory concentration) of compound W12, W26 and W27 against pseudotyped virus EBOV. Serial 2-fold dilutions of compound from 0.5 µM to 32 µM were evaluated.</p>
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<p>IC<sub>50</sub> analysis of compound W12, W26 and W27 against pseudotyped MARV. Serial 2-fold dilutions of compound from 0.5 µM to 32 µM were evaluated.</p>
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<p>IC<sub>50</sub> analysis of compound W12, W26 and W27 against infectious virus EBOV and MARV in human Huh7 cells. Compound concentrations from 0.1 µM to 100 µM were evaluated. The toxicity was also evaluated from 0.1 µM to 100 µM of compound concentrations. Remdesivir was used as positive controls.</p>
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<p>Specificity testing of compound W12 and W26 against different pseudotyped viruses (EBOV, MARV, HIV, VSV and A-MLV). HIV strain, HXBc2 (HX); vesicular stomatitis virus (VSV); amphitropic murine leukemia virus (A-MLV).</p>
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<p>Structural comparisons of compounds W12 (<span class="html-italic">Fumiquinazoline J</span>), W26 (<span class="html-italic">Emindole SB</span>) and W27 (<span class="html-italic">Fusaindoterpene B</span>) with the amino acid <span class="html-italic">Tryptophan</span> (Trp)-derived <span class="html-italic">N-Acetyl-L-Tryptophan</span> (Ac-L-Trp) and <span class="html-italic">N-Acetyl-D-Tryptophan</span> (Ac-D-Trp) forms. The common indole ring is in a red circle and the differences in their side groups are shown. All molecule weights (MWs) of these compounds are also shown below their structures.</p>
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<p>(<b>A</b>). Molecular docking of compounds W12, W26, W27and the amino acid Tryptophan (Trp)-derived <span class="html-italic">N-Acetyl-L-Tryptophan</span> (Ac-L-Trp) and <span class="html-italic">N-Acetyl-D-Tryptophan</span> (Ac-D-Trp) forms in the NPC1 receptor binding site of EBOV using AutoDock and illustrations using the Chimera (Surface models). (<b>B</b>). Compound W12 ribbon model (<b>left</b>) and the interactions model ((<b>right</b>), made using PyMol). All the docking scores (kcal/mol) are labeled in the models. Indole ring is in the yellow circle. Surface colors: red, hydrophobic; blue, hydrophilic.</p>
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<p>Compound binding to EBOV GP-RBD. Compound W12 binding affinity at pH 6.1 was evaluated using biolayer interferometry (BLI) assay method. (<b>A</b>). W12 direct binding to RBD of EBOV-GP. (<b>B</b>). W12 binding competition with receptor NPC1 to RBD of EBOV-GP.</p>
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13 pages, 7126 KiB  
Article
Selenium–Chondroitin Sulfate Nanoparticles Inhibit Angiogenesis by Regulating the VEGFR2-Mediated PI3K/Akt Pathway
by Xia Zheng, Xiaofei Liu, Zhuo Wang, Rui Li, Qiaoli Zhao, Bingbing Song, Kit-Leong Cheong, Jianping Chen and Saiyi Zhong
Mar. Drugs 2025, 23(1), 22; https://doi.org/10.3390/md23010022 - 2 Jan 2025
Viewed by 589
Abstract
Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate [...] Read more.
Chondroitin sulfate (CS), a class of glycosaminoglycans covalently attached to proteins to form proteoglycans, is widely distributed in the extracellular matrix and cell surface of animal tissues. In our previous study, CS was used as a template for the synthesis of seleno-chondroitin sulfate (SeCS) through the redox reaction of ascorbic acid (Vc) and sodium selenite (Na2SeO3) and we found that SeCS could inhibit tumor cell proliferation and invasion. However, its effect on angiogenesis and its underlying mechanism are unknown. In this study, we analyzed the effect of SeCS on tube formation in vitro, based on the inhibition of tube formation and migration of human umbilical vein endothelial cells (HUVECs), and evaluated the in vivo angiogenic effect of SeCS using the chick embryo chorioallantoic membrane (CAM) assay. The results showed that SeCS significantly inhibited the angiogenesis of chicken embryo urothelium. Further mechanism analysis showed that SeCS had a strong inhibitory effect on VEGFR2 expression and its downstream PI3K/Akt signaling pathway, which contributed to its anti-angiogenic effects. In summary, SeCS showed good anti-angiogenic effects in an HUVEC cell model and a CAM model, suggesting that it may be a potential angiogenesis inhibitor. Full article
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<p>Molecular structure of CS from shark.</p>
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<p>Effects of different treatments on tube formation. (<b>A</b>) Concentration-dependent vascular disruption process of CS, SeNPs, SeCS and Bev incubated with blood vessels for a 6 h period at 37 °C. (<b>B</b>) The generation rate for the number of primary nodes produced by different groups at a concentration of 200 µg/mL. (<b>C</b>) The number of junctions and the generation rate for each group at 200 µg/mL. (<b>D</b>) The total lumen branch length and the generation rate in diverse groups at 200 µg/mL. * <span class="html-italic">p</span> &lt; 0.05 and ** <span class="html-italic">p</span> &lt; 0.01 compared to the control group, respectively. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 and <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01 compared with each other of sample groups. Scale bars = 100 μm.</p>
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<p>(<b>A</b>) HMEC-1 cells were subjected to tube formation assay with 200 μg/mL of CS, SeNPs, SeCS and Bev. (<b>B</b>) The generation rate for the number of primary nodes produced by different groups at a concentration of 200 µg/mL. * <span class="html-italic">p</span> &lt; 0.05 compared to the control group, respectively. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05 compared with each other of sample groups. Scale bars = 100 μm.</p>
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<p>Effects of CS, SeNPs, SeCS and Bev at 200 µg/mL on the cell viability of HUVECs.</p>
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<p>Effects of different treatments on wound healing ability of HUVECs. (<b>A</b>) Micrographs of scratched HUVECs treated with 200 μg/mL CS, SeNPs, SeCS and Bev for 0 and 24 h (200×). (<b>B</b>) Histogram of scratch healing rate of HUVECs. **** <span class="html-italic">p</span> &lt; 0.0001 compared to the control group, respectively. <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001, and <sup>####</sup> <span class="html-italic">p</span> &lt; 0.0001 compared with each of the other sample groups.</p>
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<p>Effects of different treatments on invasion ability of HUVECs. (<b>A</b>) Invasion of HUVECs treated with 200 μg/mL CS, SeNPs, SeCS and Bev for 24 h (200×). (<b>B</b>) Histogram of HUVECs invasion rate. **** <span class="html-italic">p</span> &lt; 0.0001 compared to the control group, respectively. <sup>####</sup> <span class="html-italic">p</span> &lt; 0.0001 compared with each of the other sample groups.</p>
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<p>Effects of CS, SeNPs, SeCS and Bev at 200 µg/mL on the suppression of angiogenesis in a CAM model. (<b>A</b>) Images of CAMs treated with the same concentration for 48 h. (<b>B</b>) The rate of inhibition of chick embryo allantoic membrane angiogenesis (<span class="html-italic">n</span> = 50). * <span class="html-italic">p</span> &lt; 0.05 compared to the control group, respectively.</p>
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<p>Expression levels of VEGFR2 and PI3K/Akt signaling pathway proteins by Western blot. (<b>A</b>) Band chart of VEGFR2, FAK and PI3K proteins expression. (<b>B</b>) Band chart of p-eNOS/eNOS and p-Akt/Akt proteins expression. (<b>C</b>–<b>G</b>) Bar charts of VEGFR2, FAK, PI3K, p-eNOS/eNOS and p-Akt/Akt protein expression (<span class="html-italic">n</span> = 3). * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01 compared to the control group, respectively. <sup>#</sup> <span class="html-italic">p</span> &lt; 0.05, <sup>##</sup> <span class="html-italic">p</span> &lt; 0.01, <sup>###</sup> <span class="html-italic">p</span> &lt; 0.001 compared with each of the other sample groups.</p>
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<p>Signaling pathway diagram of SeCS inhibition of angiogenesis.</p>
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13 pages, 1677 KiB  
Article
Pilot-Scale Enzymatic Conversion of Low Stability, High Free Fatty, Squid Oil to an Oxidatively Stable Astaxanthin-Rich Acylglyceride Oil Suitable for Nutritional Applications
by Asavari Joshi, Brendan Holland, Moninder Sachar and Colin J. Barrow
Mar. Drugs 2025, 23(1), 21; https://doi.org/10.3390/md23010021 - 2 Jan 2025
Viewed by 444
Abstract
Squid viscera, a byproduct of squid processing, contains oil rich in omega-3 fatty acids (up to 10% by mass) and the antioxidant astaxanthin. However, its high free fatty acid (FFA) content compromises stability. To address this, pilot-scale (200 L) enzymatic re-esterification of squid [...] Read more.
Squid viscera, a byproduct of squid processing, contains oil rich in omega-3 fatty acids (up to 10% by mass) and the antioxidant astaxanthin. However, its high free fatty acid (FFA) content compromises stability. To address this, pilot-scale (200 L) enzymatic re-esterification of squid oil using immobilized lipase (Lipozyme RMIM) was demonstrated, resulting in high acylglyceride yields. The processed oil was analyzed for oxidation kinetics and thermodynamics using Rancimat, fatty acid composition using GC, omega-3 fatty acid positional distribution in the acylglyceride product using 13C NMR, and astaxanthin content. Lipase treatment reduced FFA levels from 44% to 4% and increased acylglycerides to 93% in squid oil. This reduction in FFA was accompanied by significantly increased stability (0.06 to 18.9 h by Rancimat). The treated oil showed no loss in astaxanthin (194.1 µg/g) or omega-3 fatty acids, including docosahexaenoic acid (DHA). DHA remaining predominantly at sn-2 indicated that the naturally occurring positional distribution of this omega-3 FFA was retained in the product. Lipase treatment significantly enhanced oxidative stability, evidenced by improved thermodynamic parameters (Ea 94.15 kJ/mol, ΔH 91.09 kJ/mol, ΔS −12.6 J/mol K) and extended shelf life (IP25 74.42 days) compared to starting squid oil and commercial fish/squid oils lacking astaxanthin. Thus, lipase treatment offers an effective strategy for reducing FFA levels and producing oxidatively stable, astaxanthin-rich acylglyceride squid oil with DHA retained at the nutritionally favored sn-2 position. Full article
(This article belongs to the Special Issue Marine Anti-Inflammatory and Antioxidant Agents, 4th Edition)
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<p>Lipid oxidation parameters of enzyme-processed squid oil using Rancimat.</p>
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<p>Free fatty acid reduction profile of lipase-processed squid visceral oil (ESO). Results are presented as mean ± SD.</p>
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<p>Carbonyl region of <sup>13</sup>C NMR of lipase-treated squid visceral oil illustrating positional distribution of fatty acids. Abbreviations: DHA (docosahexaenoic acid), EPA (eicosapentaenoic acid), SDA (stearidonic acid), DPA (docosapentaenoic acid), ETA (eicosatetraenoic acid), MUFA (monounsaturated fatty acids), and SFA (saturated fatty acids).</p>
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<p>(<b>a</b>) Induction period (IP) of the oils against temperature (CCO—commercial calamari oil; CFO—commercial fish oil; ESO—enzymatically re-esterified squid output oil); (<b>b</b>) kinetic rate constant (k) of lipid oxidation of the CCO, CFO, and SE. Results are presented as mean ± SD. The bars not sharing common lowercase letters (labelled on the top of each bar) for each temperature in (<b>a</b>) and each oil in (<b>b</b>) are significantly different (<span class="html-italic">p</span> &lt; 0.05).</p>
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40 pages, 14151 KiB  
Review
Syntheses of Marine Natural Products via Matteson Homologations and Related Processes
by Uli Kazmaier
Mar. Drugs 2025, 23(1), 20; https://doi.org/10.3390/md23010020 - 2 Jan 2025
Viewed by 447
Abstract
Matteson homologation, a successive extension of chiral boronic esters, is perfectly suited for the synthesis of complex molecular structures containing several stereogenic centers. The “classical version” allows the introduction of various functional groups in a 1,2-anti-configuration. The absolute configuration is determined [...] Read more.
Matteson homologation, a successive extension of chiral boronic esters, is perfectly suited for the synthesis of complex molecular structures containing several stereogenic centers. The “classical version” allows the introduction of various functional groups in a 1,2-anti-configuration. The absolute configuration is determined by the choice of the chiral auxiliary, which can be used to introduce several stereogenic centers. In contrast, in Aggarwal’s lithiation-borylation strategy, new chiral auxiliary reagents must be used in each reaction step, which on the other hand allows the individual insertion of the desired stereogenic centers. Both methods have their individual advantages and disadvantages and are well suited for the synthesis of marine natural products. Full article
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<p>Marine cyclodepsipeptides.</p>
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<p>Tautomycin.</p>
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<p>Selected apratoxins.</p>
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<p>Retrosynthesis of bastimolide B.</p>
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<p>Nucleophilic substitution of α-bromoboronic esters according to Matteson et al. [<a href="#B19-marinedrugs-23-00020" class="html-bibr">19</a>].</p>
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<p>Matteson homologations using pinanediol as chiral auxiliary.</p>
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<p>Mechanism of Matteson homologation.</p>
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<p>Sequential double diastereo-differentiation by using C<sub>2</sub>-symmetric diols as auxiliary according to Matteson et al. [<a href="#B33-marinedrugs-23-00020" class="html-bibr">33</a>].</p>
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<p>Lithiation-borylation of Hoppe carbamates according to Aggarwal et al. [<a href="#B50-marinedrugs-23-00020" class="html-bibr">50</a>].</p>
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<p>Lithiation-borylation of secondary Hoppe carbamates according to Aggarwal et al. [<a href="#B63-marinedrugs-23-00020" class="html-bibr">63</a>].</p>
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<p>Sparteine-free homologation according to Kalesse et al. [<a href="#B66-marinedrugs-23-00020" class="html-bibr">66</a>].</p>
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<p>Sparteine-free homologation according to Blakemore et al. [<a href="#B69-marinedrugs-23-00020" class="html-bibr">69</a>,<a href="#B70-marinedrugs-23-00020" class="html-bibr">70</a>].</p>
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<p>Catalytic, enantioselective homologation according to Jacobsen et al. [<a href="#B82-marinedrugs-23-00020" class="html-bibr">82</a>,<a href="#B83-marinedrugs-23-00020" class="html-bibr">83</a>,<a href="#B84-marinedrugs-23-00020" class="html-bibr">84</a>].</p>
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<p>Synthesis of dictyopterene A according to Pietruszka et al. [<a href="#B98-marinedrugs-23-00020" class="html-bibr">98</a>].</p>
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<p>Synthesis of awajanomycin according to Koert et al. [<a href="#B100-marinedrugs-23-00020" class="html-bibr">100</a>].</p>
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<p>Synthesis of danicalipin A according to Burns et al. [<a href="#B102-marinedrugs-23-00020" class="html-bibr">102</a>].</p>
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<p>Synthesis of motuporin according to Armstrong et al. [<a href="#B114-marinedrugs-23-00020" class="html-bibr">114</a>].</p>
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<p>Synthesis of callipeltin A according to Horn and Kazmaier [<a href="#B123-marinedrugs-23-00020" class="html-bibr">123</a>,<a href="#B124-marinedrugs-23-00020" class="html-bibr">124</a>].</p>
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<p>Synthesis of tautomycin according to Maurer and Armstrong [<a href="#B128-marinedrugs-23-00020" class="html-bibr">128</a>].</p>
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<p>Synthesis of emericellamide A according to Priester and Kazmaier [<a href="#B132-marinedrugs-23-00020" class="html-bibr">132</a>].</p>
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<p>Synthesis of lagunamide A according to Gorges and Kazmaier [<a href="#B24-marinedrugs-23-00020" class="html-bibr">24</a>].</p>
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<p>Synthesis of polyketide fragment <b>74</b> according to Andler and Kazmaier [<a href="#B143-marinedrugs-23-00020" class="html-bibr">143</a>].</p>
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<p>Syntheses of apratoxins A and B according to Andler and Kazmaier [<a href="#B152-marinedrugs-23-00020" class="html-bibr">152</a>].</p>
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<p>Synthesis of doliculide according to Kazmaier et al. [<a href="#B44-marinedrugs-23-00020" class="html-bibr">44</a>].</p>
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<p>Synthesis of soledanolactone E according to Aggarwal et al. [<a href="#B169-marinedrugs-23-00020" class="html-bibr">169</a>].</p>
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<p>Synthesis of soledanolactone F according to Robinson and Aggarwal [<a href="#B171-marinedrugs-23-00020" class="html-bibr">171</a>].</p>
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<p>Synthesis of erogorgiaene and stereoisomers according to Aggarwal et al. [<a href="#B175-marinedrugs-23-00020" class="html-bibr">175</a>].</p>
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<p>Synthesis of sporochnol A according to Aggarwal et al. [<a href="#B180-marinedrugs-23-00020" class="html-bibr">180</a>].</p>
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<p>Synthesis of debromoaplysin and aplysin according to Aggarwal et al. [<a href="#B184-marinedrugs-23-00020" class="html-bibr">184</a>].</p>
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<p>Generation of “diamine-free” chiral lithiated primary carbamates <b>111</b>.</p>
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<p>Synthesis of filiformin according to Aggarwal et al. [<a href="#B186-marinedrugs-23-00020" class="html-bibr">186</a>].</p>
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<p>Synthesis of kalkitoxin according to Aggarwal et al. [<a href="#B192-marinedrugs-23-00020" class="html-bibr">192</a>,<a href="#B193-marinedrugs-23-00020" class="html-bibr">193</a>].</p>
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<p>Synthesis of clavosolide A according to Aggarwal et al. [<a href="#B197-marinedrugs-23-00020" class="html-bibr">197</a>].</p>
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<p>Syntheses of baulamycin A and B according to Aggarwal et al. [<a href="#B199-marinedrugs-23-00020" class="html-bibr">199</a>].</p>
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<p>Syntheses of bastimolide fragment <b>128</b>.</p>
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<p>Syntheses of bastimolide B according to Aggarwal et al. [<a href="#B203-marinedrugs-23-00020" class="html-bibr">203</a>].</p>
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<p>Syntheses of rakicidin F according to Aggarwal et al. [<a href="#B216-marinedrugs-23-00020" class="html-bibr">216</a>].</p>
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26 pages, 2576 KiB  
Article
Wild or Reared? Cassiopea andromeda Jellyfish as a Potential Biofactory
by Stefania De Domenico, Andrea Toso, Gianluca De Rinaldis, Marta Mammone, Lara M. Fumarola, Stefano Piraino and Antonella Leone
Mar. Drugs 2025, 23(1), 19; https://doi.org/10.3390/md23010019 - 1 Jan 2025
Viewed by 1123
Abstract
The zooxanthellate jellyfish Cassiopea andromeda (Forsskål, 1775), a Lessepsian species increasingly common in the western and central Mediterranean Sea, was investigated here to assess its potential as a source of bioactive compounds from medusa specimens both collected in the wild (the harbor of [...] Read more.
The zooxanthellate jellyfish Cassiopea andromeda (Forsskål, 1775), a Lessepsian species increasingly common in the western and central Mediterranean Sea, was investigated here to assess its potential as a source of bioactive compounds from medusa specimens both collected in the wild (the harbor of Palermo, NW Sicily) and reared under laboratory-controlled conditions. A standardized extraction protocol was used to analyze the biochemical composition of the two sampled populations in terms of protein, lipid, and pigment contents, as well as for their relative concentrations of dinoflagellate symbionts. The total extracts and their fractions were also biochemically characterized and analyzed for their in vitro antioxidant activity to quantify differences in functional compounds between wild and reared jellyfish. The two populations were similar in terms of extract yield, but with substantial differences in biomass, the number of zooxanthellae, protein and lipid contents, and fatty acid composition. The hydroalcoholic extracts obtained from jellyfish grown under controlled conditions showed greater antioxidant activity due to the presence of a higher content of bioactive compounds compared to wild jellyfish. This study could be the basis for considering the sustainable breeding of this holobiont or other similar organisms as a source of valuable compounds that can be used in the food, nutraceutical, or pharmaceutical sectors. Full article
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<p>(<b>A</b>) <span class="html-italic">Cassiopea andromeda</span> collected from the port of Palermo (wild) and (<b>B</b>) <span class="html-italic">C. andromeda</span> born by strobilation and raised in the aquarium under controlled laboratory conditions (reared).</p>
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<p>SDS-PAGE analysis of proteins from wild and reared <span class="html-italic">Cassiopea andromeda</span> holobionts imaged with ChemiDoc MP Imaging System (<b>A</b>) or stained with Coomassie Brilliant Blue (<b>B</b>). MW: molecular-weight size marker; WJ: whole-jellyfish proteins; ExDW: 80% EtOH soluble proteins; P: insoluble proteins hydrolyzed with pepsin; C: insoluble proteins hydrolyzed with collagenase. Each line was loaded with 20 mg of proteins.</p>
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<p>Protein (<b>A</b>) and total phenolic (<b>B</b>) contents evaluated in hydroalcoholic extracts (ExDW), upper phases (UP), and lower phases (LP) from wild and reared jellyfish, expressed as mg of proteins per g of ExDW and mg GAE/g of ExDW. Data between the two groups of samples were analyzed by unpaired <span class="html-italic">t</span>-test (two-tailed, <span class="html-italic">p</span> &lt; 0.05). One-way ANOVA test (<span class="html-italic">p</span> &lt; 0.05) was used to compare the data in all the phases (UPs and LPs). Different letters indicate significant differences.</p>
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<p>Antioxidant activity in total 80% ethanol extracts (ExDW) and in their fractions (upper phase, UP, and lower phase, LP) from wild and reared jellyfish, expressed as nmol TE per g of ExDW. Data between the two groups of samples were analyzed by an unpaired <span class="html-italic">t</span>-test (two-tailed <span class="html-italic">p</span> value); a one-way ANOVA test was used to compare the data in all the phases (UP and LP). Different letters indicate significant differences.</p>
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14 pages, 2393 KiB  
Article
Salicylic Acid Improved the Growth of Dunaliella salina and Increased the Proportion of 9-cis-β-Carotene Isomers
by Shuaicheng Xiang, Xiaoting Qiu, Xiaojun Yan, Roger Ruan and Pengfei Cheng
Mar. Drugs 2025, 23(1), 18; https://doi.org/10.3390/md23010018 - 1 Jan 2025
Viewed by 587
Abstract
Dunaliella salina is an important source of natural β-carotene (containing 9-cis and all trans isomers) for industrial production. The phytohormone salicylic acid (SA) has been proven to have impacts on the stress resistance of higher plants, but research on microalgae is currently unclear. [...] Read more.
Dunaliella salina is an important source of natural β-carotene (containing 9-cis and all trans isomers) for industrial production. The phytohormone salicylic acid (SA) has been proven to have impacts on the stress resistance of higher plants, but research on microalgae is currently unclear. In this study, the effects of SA on the growth, biochemical composition, antioxidant enzyme activity, key enzymes of β-carotene synthesis, and cis-and trans-isomers of β-carotene in D. salina under different salt concentrations were investigated. The results were shown that at concentrations of 1.5, 2, and 2.5 M NaCl, the antioxidant enzyme activity and key enzymes for β-carotene synthesis in algal cells were significantly increased, but the content and proportion of 9-cis isomer in β-carotene isomers decreased. The addition of SA significantly increased the growth and antioxidant enzyme (SOD, MDA) activity, as well as the synthesis of key enzyme phytoene synthase (PSY), phytoene desaturase (PDS), and lycopene β cyclase (LCYB) of D. salina under high-salinity conditions. It is worth noting that under the treatment of SA, the proportion of 9-cis isomer in the three salt concentrations (1.5, 2, 2.5 M NaCl) significantly increased by 32.09%, 20.30%, and 11.32%, respectively. Moreover, SA can not only improve the salt tolerance of D. salina, but also increase the proportion of 9-cis isomer, with higher physiological activity in β-carotene, thereby enhancing the application value of D. salina. Full article
(This article belongs to the Special Issue Biotechnological Applications of Marine Photosynthetic Microorganisms)
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<p>The effects of salinity and SA on the growth of <span class="html-italic">D. salina</span>. (<b>a</b>) cell density, (<b>b</b>) dry weight. Note: values are mean ± SD, obtained from three independent groups. Significant differences between values were calculated at <span class="html-italic">p</span> &lt; 0.05 using a Tukey test and marked by different letters; “a–d” indicates a significant difference.</p>
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<p>The effects of salinity and SA on the biochemical components of <span class="html-italic">D. salina</span>. (<b>a</b>) the content of protein, (<b>b</b>) the content of polysaccharides, (<b>c</b>) the content of β-carotene. Note: values are mean ± SD, obtained from three independent groups. Significant differences between values were calculated at <span class="html-italic">p</span> &lt; 0.05 using a Tukey test and marked by different letters; “a–f” indicates a significant difference.</p>
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<p>The effects of phytohormones on the antioxidant activity of <span class="html-italic">D. salina</span> in response to salinity changes. (<b>a</b>) SOD, (<b>b</b>) MDA. Values are mean ± SD, obtained from three independent measurements. Significant differences between values were calculated at <span class="html-italic">p</span> &lt; 0.05 using a Tukey test and marked by different letters; “a–d” indicates a significant difference.</p>
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<p>The effects of phytohormones on key enzymes in the β-carotene synthesis of <span class="html-italic">D. salina</span>. (<b>a</b>) PSY, (<b>b</b>) PDS, (<b>c</b>) LCY-B. Note: values are mean ± SD, obtained from three independent groups. Significant differences between values were calculated at <span class="html-italic">p</span> &lt; 0.05 using a Tukey test and marked by different letters; “a–d” indicates a significant difference.</p>
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<p>(<b>a</b>) The effects of salinity and SA on the growth and β-carotene structure of <span class="html-italic">D. salina</span>; (<b>b</b>) the possible mechanism of salinity and SA affected the cell growth and β-carotene synthesis of <span class="html-italic">D. salina</span>. Note: values are mean ± SD, obtained from three independent group. Significant differences between values were calculated at <span class="html-italic">p</span> &lt; 0.05 using a Tukey test and marked by different letters; “a–c” indicates a significant difference. Red arrow represents up-regulated; blue arrow represents down-regulation.</p>
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13 pages, 56913 KiB  
Article
Deep-Sea Ecosystems as an Unexpected Source of Antibiotic Resistance Genes
by Wei Zhang, Yingdong Li, Yunmeng Chu, Hao Liu, Hongmei Jing and Qianfeng Xia
Mar. Drugs 2025, 23(1), 17; https://doi.org/10.3390/md23010017 - 31 Dec 2024
Viewed by 656
Abstract
The deep-sea ecosystem, a less-contaminated reservoir of antibiotic resistance genes (ARGs), has evolved antibiotic resistance for microbes to survive and utilize scarce resources. Research on the diversity and distribution of these genes in deep-sea environments is limited. Our metagenomics study employed short-read-based (SRB) [...] Read more.
The deep-sea ecosystem, a less-contaminated reservoir of antibiotic resistance genes (ARGs), has evolved antibiotic resistance for microbes to survive and utilize scarce resources. Research on the diversity and distribution of these genes in deep-sea environments is limited. Our metagenomics study employed short-read-based (SRB) and assembled-contig-based (ACB) methods to identify ARGs in deep-sea waters and sediments and assess their potential pathogenicity. SRB prediction was found to be more effective for studying the abundance and diversity of these genes, while combining both methods better illustrated the relationship of ARGs with the hosts. Deep-sea waters (DSW) and trenches had the highest diversity of ARGs, including β-lactams, multidrug resistance genes, and rifamycins. Mobile genetic elements, such as IncQ and RP4 plasmids, were also identified. The ratio of nonsynonymous to synonymous substitutions (pN/pS) values of these genes suggest different evolutionary strategies in response to deep-sea conditions and possible human impacts. These resistome profiles provide valuable insights into their natural origins as well as the ecological and evolutionary implications of antibiotic resistance in deep-sea ecosystems. The exploration of the global distribution of ARGs in diverse deep-sea environments is a novel approach that will assist in understanding their potential reservoirs and evolutionary mechanisms. Therefore, employing a comprehensive approach to studying ARGs is particularly necessary. Unique microbial life in deep-sea ecosystems, especially in deep-sea cold seeps sediments (DSCSS), deep-sea waters (DSW), and trench waters (TW), could be a valuable source of new antibiotics and resistance discovery. Full article
(This article belongs to the Special Issue Collection of Biosynthetic Genes from Marine Microbes)
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<p>A map of the sample locations. The orange, blue, red, green, and purple circles represent the sites of deep-sea cold seeps sediments (DSCSS), deep-sea sediments (DSS), deep-sea waters (DSW), trench sediments (TS), and trench waters (TW), respectively., and the numbers in parentheses represent the number of samples in the environments (<b>A</b>). The distribution of antibiotic resistance genes (ARGs) predicted by the short-read-based (SRB) method (<b>B</b>). The distribution of ARGs predicted by the assembled-contig-based (ACB) method (<b>C</b>). MSL stands for macrolide–lincosamide–streptogramin.</p>
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<p>Relative abundance of resistance mechanisms (<b>A</b>,<b>B</b>), antibiotics (<b>D</b>,<b>E</b>), and sites of antibiotic inhibition (<b>G</b>,<b>H</b>) predicted by the SRB and ACB methods in different environments, respectively. Venn plots of ARG types in resistance mechanisms (<b>C</b>), antibiotics (<b>F</b>), and sites of antibiotic inhibition (<b>I</b>) by the SRB and ACB methods in different environments, respectively.</p>
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<p>Heatmap showing the relative abundance of hosts and plasmids based on log10-transformed ARG data predicted by the SRB (<b>A</b>,<b>B</b>) and ACB (<b>C</b>) methods in different environments, respectively. Read counts per million is a metric used to normalize high-throughput sequencing data, primarily to convert differences in read counts between samples (e.g., different sequencing depths) into comparable data.</p>
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<p>Sankey plots showing the relationship between ARG classes and their hosts by the SRB (<b>A</b>) and ACB (<b>B</b>) methods in different environments, respectively. The number in parentheses represents the number of host species in the notes in the environment. The wider the width of the flow band, the higher the proportion of ARGs in the corresponding environment or host.</p>
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<p>Boxplot of the ratio of nonsynonymous to synonymous substitutions (pN/pS) for ARGs related to β-lactam (<b>A</b>), glycopeptide (<b>B</b>), disinfecting agents and antiseptics (<b>C</b>), multidrug (<b>D</b>), inhibition of cell wall synthesis (<b>E</b>), inhibition of protein synthesis (<b>F</b>), and inhibition of RNA and DNA synthesis (<b>G</b>) in different environments. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001.</p>
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11 pages, 606 KiB  
Article
A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates
by Takahiro Jomori, Nanami Higa, Shogo Hokama, Trianda Ayuning Tyas, Natsuki Matsuura, Yudai Ueda, Ryo Kimura, Sei Arizono, Nicole Joy de Voogd, Yasuhiro Hayashi, Mina Yasumoto-Hirose, Junichi Tanaka and Kanami Mori-Yasumoto
Mar. Drugs 2025, 23(1), 16; https://doi.org/10.3390/md23010016 - 30 Dec 2024
Viewed by 728
Abstract
Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current [...] Read more.
Leishmaniasis is a major public health problem, especially affecting vulnerable populations in tropical and subtropical regions. The disease is endemic in 90 countries, and with millions of people at risk, it is seen as one of the ten most neglected tropical diseases. Current treatments face challenges such as high toxicity, side effects, cost, and growing drug resistance. There is an urgent need for safer, affordable treatments, especially for cutaneous leishmaniasis (CL), the most common form. Marine invertebrates have long been resources for discovering bioactive compounds such as sesterterpenoids. Using bioassay-guided fractionations against cutaneous-type leishmaniasis promastigotes, we identified a novel furanosesterterpenoid, petrosaspongin from Okinawan marine sponges and a nudibranch, along with eight known sesterterpenoids, hippospongins and manoalides. The elucidated structure of petrosaspongin features a β-substituted furane ring, a tetronic acid, and a conjugated triene. The sesterterpenoids with a γ-butenolide group exhibited leishmanicidal activity against Leishmania major promastigotes, with IC50 values ranging from 0.69 to 53 μM. The structure–activity relationship and molecular docking simulation suggest that γ-lactone is a key functional group for leishmanicidal activity. These findings contribute to the ongoing search for more effective treatments against CL. Full article
(This article belongs to the Special Issue Marine-Derived Bioactive Substances and Their Mechanisms of Action)
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<p>The structures of compounds (<b>1</b>–<b>9</b>).</p>
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<p>Key 2D NMR correlations for petrosaspongin (<b>1</b>). (<b>a</b>) <sup>1</sup>H-<sup>1</sup>H COSY and key HMBC correlations. (<b>b</b>) Key NOESY correlations.</p>
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24 pages, 1100 KiB  
Article
Eco-Friendly Extraction of Phlorotannins from Padina pavonica: Identification Related to Purification Methods Towards Innovative Cosmetic Applications
by Moustapha Nour, Valérie Stiger-Pouvreau, Alain Guenneguez, Laurence Meslet-Cladière, Stéphane Cérantola, Ahmed Ali, Gaelle Simon, Abdourahman Daher and Sylvain Petek
Mar. Drugs 2025, 23(1), 15; https://doi.org/10.3390/md23010015 - 28 Dec 2024
Viewed by 645
Abstract
This study focuses on developing innovative and eco-friendly purification methods for the isolation of bioactive compounds derived from Padina pavonica, a brown abundant macroalga in Djibouti. Three distinct fractions, obtained via liquid-liquid extraction (LLE_FAE), solid-phase extraction (SPE_WE50), and flash chromatography (FC_EtOH20), were [...] Read more.
This study focuses on developing innovative and eco-friendly purification methods for the isolation of bioactive compounds derived from Padina pavonica, a brown abundant macroalga in Djibouti. Three distinct fractions, obtained via liquid-liquid extraction (LLE_FAE), solid-phase extraction (SPE_WE50), and flash chromatography (FC_EtOH20), were selected based on their high phenolic content and antioxidant activities. All fractions were also evaluated for their anti-ageing potential by assessing their ability to inhibit two vital skin-ageing enzymes, tyrosinase and elastase. Structural analysis by 1H-13C HMBC NMR and LC-MS revealed a selectivity of phlorotannins depending on the purification methods. The LLE_FAE fraction exhibited greater structural complexity, including compounds such as phloroglucinol, diphlorethol/difucol, fucophlorethol and bifuhalol, which likely contribute to its enhanced bioactivity compared to the fractions obtained by FC_EtOH20 and SPE_WE50, which were also active and enriched only in phloroglucinol and fucophlorethol. These findings highlight the impact of purification techniques on the selective enrichment of specific bioactive compounds and demonstrated the interest of FC or SPE in producing active phlorotannin-enriched fractions. These two purification methods hold strong potential for innovative cosmeceutical applications. Results are discussed regarding the use of P. pavonica as a promising marine resource in Djibouti to be used for the development of cosmetic industry. Full article
(This article belongs to the Special Issue Marine Cosmeceuticals)
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<p>Anti-ageing activities by elastase and tyrosinase inhibitions, determined on the different fractions, LLE_FAE, SPE and FC and their crude respective ASE extracts, obtained from the brown macroalga <span class="html-italic">Padina pavonica</span>. Epigallocatechin gallate (EGCG) and kojic acid are positive controls. Purified fractions which are used in our comparative study are shown by the arrows.</p>
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<p><sup>1</sup>H NMR spectra on phlorotannin-rich fractions from the brown macroalga <span class="html-italic">Padina pavonica</span> and obtained by three separate purification methods and the name of fractions into parentheses: solid phase extraction (SPE_EW50), flash-chromatography (FC_EtOH20), purification by washing and noted liquid/liquid (LLE_FAE) and comparison with the spectrum from the crude ASE extract (Accelerated Solvent Extraction).</p>
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<p>Structures of phenolic compounds identified in the brown macroalga <span class="html-italic">Padina pavonica</span> and referenced and numbered like in <a href="#marinedrugs-23-00015-t003" class="html-table">Table 3</a>.</p>
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24 pages, 1381 KiB  
Article
Enzymatic Hydrolysis Systems Enhance the Efficiency and Biological Properties of Hydrolysates from Frozen Fish Processing Co-Products
by Maria Sapatinha, Carolina Camacho, Antónia Juliana Pais-Costa, Ana Luísa Fernando, António Marques and Carla Pires
Mar. Drugs 2025, 23(1), 14; https://doi.org/10.3390/md23010014 - 28 Dec 2024
Viewed by 551
Abstract
Co-products from the frozen fish processing industry often lead to financial losses. Therefore, it is essential to transform these co-products into profitable goods. This study explores the production of fish protein hydrolysates (FPH) from three co-products: the heads and bones of black scabbardfish [...] Read more.
Co-products from the frozen fish processing industry often lead to financial losses. Therefore, it is essential to transform these co-products into profitable goods. This study explores the production of fish protein hydrolysates (FPH) from three co-products: the heads and bones of black scabbardfish (Aphanopus carbo), the carcasses of gilthead seabream (Sparus aurata), and the trimmings of Nile perch (Lates niloticus). Four enzymatic hydrolysis systems were tested: an endopeptidase (Alcalase, A), an exopeptidase (Protana, P), two-stage hydrolysis with an endopeptidase followed by an exopeptidase (A + P), and a single stage with endo- and exopeptidase (AP). The results show that combined enzymatic treatments, especially single-stage Alcalase and Protana (AP), achieved high protein yields (80%) and enhanced degrees of hydrolysis (34 to 49%), producing peptides with lower molecular weights. FPH exhibited significant antioxidant activity, in 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, with EC50 values below 5 mg/mL. Additionally, AP hydrolysates demonstrated over 60% angiotensin-converting enzyme (ACE) inhibition at 5 mg/mL, indicating potential antihypertensive applications. Antidiabetic and anti-Alzheimer activities were present, but at relatively low levels. AP hydrolysates, especially from gilthead seabream, proved to be the most promising. This study highlights the value of fish co-products as sources of functional peptides, contributing to waste reduction, and their potential applications in food, agriculture, and nutraceuticals. Full article
(This article belongs to the Special Issue Value-Added Products from Marine Fishes)
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<p>Degree of hydrolysis ((<b>a</b>), DH) and yield of the hydrolysate ((<b>b</b>), Yh) process of gilthead seabream carcass (GB) with Alcalase and Protana (AP and A + P) over time.</p>
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<p>Size exclusion chromatograms of fish protein hydrolysates of gilthead seabream (GB) prepared with Alcalase and Protana (AP) at three different stages of hydrolysis (0 min, 180 min, and 360 min). Peaks separated by molecular weight ranges (&gt;1000 Da, &gt;500 Da, &lt;500 Da, &lt;100 Da).</p>
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<p>Antioxidant assays (DPPH, ABTS, reducing power (RP)) with different hydrolysates prepared with black scabbardfish heads and bones (BS), gilthead seabream carcass (GB) and Nile perch trimmings (NP) using various enzyme combinations: Alcalase (A), Protana (P), Alcalase followed by Protana (A + P), and Alcalase and Protana added simultaneously (AP). The columns represent the mean values, and different letters represent significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>Iron (<b>a</b>) and cooper (<b>b</b>) chelation activity with different hydrolysates prepared with black scabbardfish heads and bones (BS), gilthead seabream carcass (GB) and Nile perch trimmings (NP) using various enzyme combinations: Alcalase (A), Protana (P), Alcalase followed by Protana (A + P), and Alcalase and Protana added simultaneously (AP). n.d. indicates values that could not be determined for the samples. The columns represent the mean values, and different letters reveal significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>IC<sub>50</sub> values for α-Amylase inhibitory activity and α-glucosidase inhibition percentages (%) with 50 mg/mL of FPH prepared from black scabbardfish heads and bones (BS), gilthead seabream carcass (GB) and Nile perch trimmings (NP) using various enzyme combinations: Alcalase (A), Protana (P), Alcalase followed by Protana (A + P), and Alcalase and Protana added simultaneously (AP). ‘n.d.’ indicates values that could not be determined for the samples. The columns represent the mean values, and different letters indicate significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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<p>AChE inhibition percentages (%) with 50 mg/mL and ACE inhibition percentages (%) with 5 mg/mL of FPH prepared from black scabbardfish heads and bones (BS), gilthead seabream carcass (GB) and Nile perch trimmings (NP) using various enzyme combinations: Alcalase (A), Protana (P), Alcalase followed by Protana (A + P), and Alcalase and Protana added simultaneously (AP). ‘n.d.’ indicates values that could not be determined for the samples. The columns represent the mean values, and different letters significant differences (<span class="html-italic">p</span> &lt; 0.05).</p>
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