Molecules

353 KiB

Open AccessArticle

Antifungal Compounds Produced by Colletotrichum gloeosporioides, an Endophytic Fungus from Michelia champaca

by Vanessa Mara Chapla, Maria Luiza Zeraik, Ioanis Hcristos Leptokarydis, Geraldo Humberto Silva, Vanderlan Silva Bolzani, Maria Claudia M. Young, Ludwig Heinrich Pfenning and Angela Regina Araújo

Molecules 2014, 19(11), 19243-19252; https://doi.org/10.3390/molecules191119243 - 21 Nov 2014

Cited by 63 | Viewed by 9539

Abstract

In this study, eight endophytic fungi were isolated from the leaves, stems and roots of Michelia champaca. The isolates were screened and evaluated for their antifungal, anticancer and acetylcholinesterase (AChE) inhibitory activities. All of the extracts exhibited potent activity against two evaluated [...] Read more.

In this study, eight endophytic fungi were isolated from the leaves, stems and roots of Michelia champaca. The isolates were screened and evaluated for their antifungal, anticancer and acetylcholinesterase (AChE) inhibitory activities. All of the extracts exhibited potent activity against two evaluated phytopathogenic fungi. Chemical investigation of EtOAc extracts of the endophytic fungus Colletotrichum gloeosporioides resulted in the isolation of one new compound, 2-phenylethyl 1H-indol-3-yl-acetate (1), and seven known compounds: uracil (2), cyclo-(S*-Pro-S*-Tyr) (3), cyclo-(S*-Pro-S*-Val) (4), 2(2-aminophenyl)acetic acid (5), 2(4-hydroxyphenyl)acetic acid (6), 4-hydroxy- benzamide (7) and 2(2-hydroxyphenyl)acetic acid (8). All of the compound structures were elucidated using 1D and 2D NMR and MS analyses. The antifungal and AChE inhibitory activities of compounds 1–8 were evaluated in vitro. Compound 1 exhibited promising activity against Cladosporium cladosporioides and C. sphaerospermum that was comparable to that of the positive control nystatin. Full article

(This article belongs to the Section Natural Products Chemistry)

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615 KiB

Open AccessArticle

Volatile Profiling of Aromatic Traditional Medicinal Plant, Polygonum minus in Different Tissues and Its Biological Activities

by Rafidah Ahmad, Syarul Nataqain Baharum, Hamidun Bunawan, Minki Lee, Normah Mohd Noor, Emelda Roseleena Rohani, Norashikin Ilias and Noraziah Mohamad Zin

Molecules 2014, 19(11), 19220-19242; https://doi.org/10.3390/molecules191119220 - 20 Nov 2014

Cited by 61 | Viewed by 9966

Abstract

The aim of this research was to identify the volatile metabolites produced in different organs (leaves, stem and roots) of Polygonum minus, an important essential oil producing crop in Malaysia. Two methods of extraction have been applied: Solid Phase Microextraction (SPME) and [...] Read more.

The aim of this research was to identify the volatile metabolites produced in different organs (leaves, stem and roots) of Polygonum minus, an important essential oil producing crop in Malaysia. Two methods of extraction have been applied: Solid Phase Microextraction (SPME) and hydrodistillation coupled with Gas Chromatography-Mass Spectrometry (GC-MS). Approximately, 77 metabolites have been identified and aliphatic compounds contribute significantly towards the aroma and flavour of this plant. Two main aliphatic compounds: decanal and dodecanal were found to be the major contributor. Terpenoid metabolites were identified abundantly in leaves but not in the stem and root of this plant. Further studies on antioxidant, total phenolic content, anticholinesterase and antimicrobial activities were determined in the essential oil and five different extracts. The plant showed the highest DPPH radical scavenging activity in polar (ethanol) extract for all the tissues tested. For anti-acetylcholinesterase activity, leaf in aqueous extract and methanol extract showed the best acetylcholinesterase inhibitory activities. However, in microbial activity, the non-polar extracts (n-hexane) showed high antimicrobial activity against Methicillin-resistant Staphylococcus aureus (MRSA) compared to polar extracts. This study could provide the first step in the phytochemical profiles of volatile compounds and explore the additional value of pharmacology properties of this essential oil producing crop Polygonum minus. Full article

(This article belongs to the Section Metabolites)

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1822 KiB

Open AccessArticle

Discovery of Novel Small-Molecule Compounds with Selective Cytotoxicity for Burkitt’s Lymphoma Cells Using 3D Ligand-Based Virtual Screening

by Martina Gobec, Izidor Sosič, Boris Brus, Aleš Obreza, Stanislav Gobec and Irena Mlinarič-Raščan

Molecules 2014, 19(11), 19209-19219; https://doi.org/10.3390/molecules191119209 - 19 Nov 2014

Viewed by 7325

Abstract

We describe a ligand-based approach towards compounds with more specific targeting for Burkitt’s lymphoma. Using three-dimensional ligand-based similarity searches and a previously described hit compound, we have identified six compounds that are chemically different but with similar spatial conformations. Biological evaluation revealed that [...] Read more.

We describe a ligand-based approach towards compounds with more specific targeting for Burkitt’s lymphoma. Using three-dimensional ligand-based similarity searches and a previously described hit compound, we have identified six compounds that are chemically different but with similar spatial conformations. Biological evaluation revealed that one compound has better growth inhibition and improved selectivity towards Burkitt’s lymphoma cells than the query compound. However, initial mechanism-of-action studies show a different target profile in comparison with the previous hit compound, which does not involve the inhibition of the proteasome or the NFκB pathway. The data from this study provide a solid basis for further efforts in the search for selective agents against Burkitt’s lymphoma. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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(A) Shape and features of compound SPI-15, as perceived by the rapid overlay of chemical structures (ROCS) software; (B) Structural formulae of SPI-15 and its spatial analogs investigated here with their TanimotoCombo scores, Compounds 1–6, T = TanimotoCombo score. Full article ">Figure 2
(A) Ramos, Thp-1, Jurkat, MCF-7, and PC3 cells were incubated with vehicle (control) and 25 µM Compounds 1–6 for 24 h. The data are the residual metabolic activities expressed as percentages relative to the control cells, as means (±SD) from three independent experiments, each conducted in triplicate; (B) Cell cycle analysis of Ramos cells after 24 h treatment with vehicle (NT), Compound 2 and SPI-15 (as indicated). The data are representative of a single experiment, of three independent experiments. Full article ">Figure 2 Cont.
(A) Ramos, Thp-1, Jurkat, MCF-7, and PC3 cells were incubated with vehicle (control) and 25 µM Compounds 1–6 for 24 h. The data are the residual metabolic activities expressed as percentages relative to the control cells, as means (±SD) from three independent experiments, each conducted in triplicate; (B) Cell cycle analysis of Ramos cells after 24 h treatment with vehicle (NT), Compound 2 and SPI-15 (as indicated). The data are representative of a single experiment, of three independent experiments. Full article ">Figure 3
(A) Determination of annexin-V-positive and propidium-iodide-positive Ramos cells after treatment with vehicle (NT) and 10 µM and 25 µM Compound 2 (as indicated) for 24 h, with analysis by flow cytometry. The data are representative of a single experiment, of three independent experiments; (B) Ramos cells were treated for 4, 8, 16, and 24 h with vehicle (NT) and 25 µM Compound 2. Caspase 3/7 activity was determined spectrofluorometrically by measuring cleavage of Ac-DEVD.AFC in whole-cell lysates. The data are changes in fluorescence with time, as means (±SD) from three independent experiments, each conducted in triplicate. *, p < 0.05, versus relevant vehicle control; (C) Analysis of annexin-V/propidium-iodide–positive cells after 24 h treatment with 10 µM and 25 µM Compound 2 in the absence and presence of 50 µM zVADfmk. The data are means (±SD) from three independent experiments, each conducted in triplicate. Full article ">Figure 4
The 20S human proteasome activities were determined spectrofluorometrically according to the cleavage of the substrate. The chymotrypsin-like (A); trypsin-like (B); and caspase-like (C); (D) Determination of SEAP activity in Ramos-blue cells after pre-treatment for 1 h with vehicle, 5 µM and 10 µM Compound 2 or 10 µM SPI-15, and subsequently adding 50 ng/mL TNFα. After 16 h, the supernatants were collected and the SEAP activities were determined. The data are means (±SD) from three independent experiments, each conducted in triplicate. Full article ">Figure 5
Structural formula of hit compound 2. Full article ">

677 KiB

Open AccessReview

Antioxidant Property of Coffee Components: Assessment of Methods that Define Mechanisms of Action

by Ningjian Liang and David D. Kitts

Molecules 2014, 19(11), 19180-19208; https://doi.org/10.3390/molecules191119180 - 19 Nov 2014

Cited by 419 | Viewed by 35180

Abstract

Coffee is a rich source of dietary antioxidants, and this property, coupled with the fact that coffee is one of the world’s most popular beverages, has led to the understanding that coffee is a major contributor to dietary antioxidant intake. Brewed coffee is [...] Read more.

Coffee is a rich source of dietary antioxidants, and this property, coupled with the fact that coffee is one of the world’s most popular beverages, has led to the understanding that coffee is a major contributor to dietary antioxidant intake. Brewed coffee is a complex food matrix with numerous phytochemical components that have antioxidant activity capable of scavenging free radicals, donating hydrogen and electrons, providing reducing activity and also acting as metal ion pro-oxidant chelators. More recent studies have shown that coffee components can trigger tissue antioxidant gene expression and protect against gastrointestinal oxidative stress. This paper will describe different in vitro, cell-free and cell-based assays that both characterize and compare the antioxidant capacity and mechanism of action of coffee and its bioactive constituents. Moreover, evidence of cellular antioxidant activity and correlated specific genomic events induced by coffee components, which are relevant to antioxidant function in both animal and human studies, will be discussed. Full article

(This article belongs to the Special Issue Free Radicals and Radical Ions)

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456 KiB

Open AccessArticle

Anti-Cholinesterase Activity of Lycopodium Alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis

by Nguyen Ngoc Chuong, Nguyen Thi Thu Huong, Tran Manh Hung and Tran Cong Luan

Molecules 2014, 19(11), 19172-19179; https://doi.org/10.3390/molecules191119172 - 19 Nov 2014

Cited by 18 | Viewed by 8724

Abstract

A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. [...] Read more.

A series of Lycopodium alkaloids, namely lycosquarosine A (1), acetylaposerratinine (2), huperzine A (3), huperzine B (4), 8α-hydrophlemariurine B (5), and huperzinine (6), has been isolated from Vietnamese Huperzia squarrosa. Among them, lycosquarosine A (1) is the new metabolite of the natural source. Lycosquarosine A completely inhibited AChE activity in a dose dependent manner with an IC₅₀ value of 54.3 μg/mL, while acetylaposerratinine (2) showed stronger inhibitory activity than 1 with an IC₅₀ value of 15.2 µg/mL. This result indicates that these alkaloids may be a potent source of AChE inhibitors. Full article

(This article belongs to the Collection Bioactive Compounds)

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1756 KiB

Open AccessArticle

Spectral and Kinetic Properties of Radicals Derived from Oxidation of Quinoxalin-2-One and Its Methyl Derivative

by Konrad Skotnicki, Julio R. De la Fuente, Alvaro Cañete and Krzysztof Bobrowski

Molecules 2014, 19(11), 19152-19171; https://doi.org/10.3390/molecules191119152 - 19 Nov 2014

Cited by 7 | Viewed by 8444

Abstract

The kinetics and spectral characteristics of the transients formed in the reactions of ^•OH and ^•N₃ with quinoxalin-2(1H)-one (Q), its methyl derivative, 3-methylquinoxalin-2(1H)-one (3-MeQ) and pyrazin-2-one (Pyr) were studied by pulse radiolysis in aqueous solutions at [...] Read more.

The kinetics and spectral characteristics of the transients formed in the reactions of ^•OH and ^•N₃ with quinoxalin-2(1H)-one (Q), its methyl derivative, 3-methylquinoxalin-2(1H)-one (3-MeQ) and pyrazin-2-one (Pyr) were studied by pulse radiolysis in aqueous solutions at pH 7. The transient absorption spectra recorded in the reactions of ^•OH with Q and 3-MeQ consisted of an absorption band with λ_max = 470 nm assigned to the OH-adducts on the benzene ring, and a second band with λ_max = 390 nm (for Q) and 370 nm (for 3-MeQ) assigned, inter alia, to the N-centered radicals on a pyrazin-2-one ring. The rate constants of the reactions of ^•OH with Q and 3-MeQ were found to be in the interval (5.9–9.7) × 10⁹ M^–1·s^–1 and were assigned to their addition to benzene and pyrazin-2-one rings and H-abstraction from the pyrazin-2-one nitrogen. In turn, the transient absorption spectrum observed in the reaction of ^•N₃ exhibits an absorption band with λ_max = 350 nm. This absorption was assigned to the N-centered radical on the Pyr ring formed after deprotonation of the respective radical cation resulting from one-electron oxidation of 3-MeQ. The rate constant of the reaction of ^•N₃ with 3 MeQ was found to be (6.0 ± 0.5) × 10⁹ M^–1·s^–1. Oxidation of 3-MeQ by ^•N₃ and Pyr by ^•OH and ^•N₃ confirms earlier spectral assignments. With the rate constant of the ^•OH radical with Pyr (k = 9.2 ± 0.2) × 10⁹ M^–1·s^‒1, a primary distribution of the ^•OH attack was estimated nearly equal between benzene and pyrazin-2-one rings. Full article

(This article belongs to the Special Issue Free Radicals and Radical Ions)

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864 KiB

Open AccessReview

Synthetic Applications of Intramolecular Thiol-Ene “Click” Reactions

by Eoin M. Scanlan, Vincent Corcé and Aoife Malone

Molecules 2014, 19(11), 19137-19151; https://doi.org/10.3390/molecules191119137 - 19 Nov 2014

Cited by 42 | Viewed by 13697

Abstract

The intermolecular thiol-ene reaction is emerging as a highly efficient; free-radical mediated “click” process with diverse applications in biofunctionalisation and materials science. The related intramolecular thiol-ene reactions offer significant potential for the preparation of a wide range of sulphur containing heterocycles including synthetic [...] Read more.

The intermolecular thiol-ene reaction is emerging as a highly efficient; free-radical mediated “click” process with diverse applications in biofunctionalisation and materials science. The related intramolecular thiol-ene reactions offer significant potential for the preparation of a wide range of sulphur containing heterocycles including synthetic therapeutics such as cyclic peptides and thiosugars. Herein, we review recent advances in intramolecular thiyl-radical mediated reactions and their applications for synthetic and medicinal chemistry. Full article

(This article belongs to the Special Issue Free Radicals and Radical Ions)

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345 KiB

Open AccessArticle

Vernonia kotschyana Roots: Therapeutic Potential via Antioxidant Activity

by Alexandru Vasincu, Berit S. Paulsen, Drissa Diallo, Ioana Vasincu, Ana C. Aprotosoaie, Veronica Bild, Christiana Charalambous, Andreas I. Constantinou, Anca Miron and Cristina M. Gavrilescu

Molecules 2014, 19(11), 19114-19136; https://doi.org/10.3390/molecules191119114 - 19 Nov 2014

Cited by 22 | Viewed by 8404

Abstract

The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts [...] Read more.

The roots of Vernonia kotschyana Sch. Bip. ex Walp. (Asteraceae) are used in Malian traditional medicine in the treatment of gastroduodenal ulcers and gastritis. Since oxidative stress is involved in gastric ulceration, the aim of this study was to screen the root extracts for their in vitro antioxidant activity and phenolic content. The roots were extracted successively with chloroform, ethyl acetate, ethanol and water. The antioxidant activity of root extracts was evaluated in both cell-free and cell-based assays. Their chemical characterization was performed by Fourier transform infrared spectroscopy (FT-IR) whereas the total phenolic content was determined by the Folin-Ciocalteu method. The ethyl acetate extract displayed the highest phenolic content and was found to be the most active in the free radical scavenging and lipid peroxidation inhibition assays; it also showed a high antioxidant activity in MCF-12F cells. This study suggests a potential use of the ethyl acetate extract of Vernonia kotschyana not only as an antioxidant agent in gastroduodenal ulcers and gastritis, but also in other disorders characterized by high levels of oxidative stress. Full article

(This article belongs to the Section Natural Products Chemistry)

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510 KiB

Open AccessArticle

Aroma-Active Compounds in Jinhua Ham Produced With Different Fermentation Periods

by Xiao-Sheng Liu, Jian-Bin Liu, Zheng-Mao Yang, Huan-Lu Song, Ye Liu and Ting-Ting Zou

Molecules 2014, 19(11), 19097-19113; https://doi.org/10.3390/molecules191119097 - 19 Nov 2014

Cited by 42 | Viewed by 7294

Abstract

The aroma-active compounds in Jinhua ham processed and stored for 9, 12, 15 and 18 months were extracted by dynamic headspace sampling (DHS) and solvent-assisted flavor evaporation (SAFE) and analyzed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS). In GC-O-MS, volatile compounds were identified based on [...] Read more.

The aroma-active compounds in Jinhua ham processed and stored for 9, 12, 15 and 18 months were extracted by dynamic headspace sampling (DHS) and solvent-assisted flavor evaporation (SAFE) and analyzed by gas chromatography-olfactometry-mass spectrometry (GC-O-MS). In GC-O-MS, volatile compounds were identified based on their mass spectrum, linear retention index (LRI), odor properties, or reference compound comparisons. The results showed that a total number of 81 aroma-active compounds were identified by GC-O-MS. Among them, acids (such as acetic acid, butanoic acid and 3-methylbutanoic acid), saturated aldehydes (such as hexanal, heptanal, octanal and 3-methylbutanal), benzene derivatives (such as benzeneacetic acid), ester and lactone (such as γ-nonalactone and γ-decalactone) were identified as critical compounds in Jinhua ham aroma. The results also indicated that the type and content of the odorants increased significantly with the duration of the fermentation period. Full article

(This article belongs to the Section Natural Products Chemistry)

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Full article ">Figure 1
Structures of the saturated and unsaturated aldehydes in Jinhua ham. Full article ">Figure 2
Structures of the ketones and alcohols in Jinhua ham. Full article ">Figure 3
Structures of the acids, esters and lactones in Jinhua ham. Full article ">Figure 4
Structures of the sulfides, benzene series compounds, pyrazines and other compounds in Jinhua ham. Full article ">Figure 5
The category of compounds in Jinhua ham by DHS. D9, D12, D15 and D18 referred to Jinhua ham processed for 9, 12, 15 and 18 months and application of DHS for aroma extraction of sample, respectively. Full article ">Figure 6
The categories of compounds in Jinhua ham by SAFE. S9, S12, S15 and S18 referred to Jinhua ham processed for 9, 12, 15 and 18 months and application of SAFE was for aroma extraction of samples, respectively. Full article ">Figure 7
Principal components loadings for different pretreatment methods. D9, D12, D15 and D18 refer to Jinhua ham processed for 9, 12, 15 and 18 months and application of DHS for aroma extraction of samples, respectively. S9, S12, S15 and S18 refer to Jinhua ham processed for 9, 12, 15 and 18 months and application of SAFE for aroma extraction of samples, respectively. Full article ">

604 KiB

Open AccessArticle

Composition and Antioxidant Activity of the Anthocyanins of the Fruit of Berberis heteropoda Schrenk

by Li-Li Sun, Wan Gao, Meng-Meng Zhang, Cheng Li, Ai-Guo Wang, Ya-Lun Su and Teng-Fei Ji

Molecules 2014, 19(11), 19078-19096; https://doi.org/10.3390/molecules191119078 - 19 Nov 2014

Cited by 23 | Viewed by 8627

Abstract

In present study, the anthocyanin composition and content of the fruit of B. heteropoda Schrenk were determined for the first time. The total anthocyanins were extracted from the fruit of B. heteropoda Schrenk using 0.5% HCl in 80% methanol and were then purified [...] Read more.

In present study, the anthocyanin composition and content of the fruit of B. heteropoda Schrenk were determined for the first time. The total anthocyanins were extracted from the fruit of B. heteropoda Schrenk using 0.5% HCl in 80% methanol and were then purified using an AB-8 macroporous resin column. The purified anthocyanin extract (PAE) was evaluated by high-performance liquid chromatography with a diode array detector (HPLC-DAD) and HPLC-high resolution-electrospray ionization-mass spectrometry (HPLC-HR-ESI-MS) under the same experimental conditions. The results revealed the presence of seven different anthocyanins. The major anthocyanins purified by preparative HPLC were confirmed to be delphinidin-3-O-glucopyranoside (30.3%), cyanidin-3-O-glucopyranoside (33.5%), petunidin-3-Ο-glucopyranoside (10.5%), peonidin-3-O-glucopyranoside (8.5%) and malvidin-3-O-glucopyranoside (13.8%) using HPLC-HR-ESI-MS and NMR spectroscopy. The total anthocyanin content was 2036.6 ± 2.2 mg/100 g of the fresh weight of B. heteropoda Schrenk fruit. In terms of its total reducing capacity assay, DPPH radical-scavenging activity assay, ferric-reducing antioxidant power (FRAP) assay and ABTS radical cation-scavenging activity assay, the PAE also showed potent antioxidant activity. The results are valuable for illuminating anthocyanins composition of B. heteropoda Schrenk and for further utilising them as a promising anthocyanin pigment source. This research enriched the chemical information of B. heteropoda Schrenk. Full article

(This article belongs to the Special Issue Anthocyanins)

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323 KiB

Open AccessArticle

Pentadecapeptide BPC 157 Enhances the Growth Hormone Receptor Expression in Tendon Fibroblasts

by Chung-Hsun Chang, Wen-Chung Tsai, Ya-Hui Hsu and Jong-Hwei Su Pang

Molecules 2014, 19(11), 19066-19077; https://doi.org/10.3390/molecules191119066 - 19 Nov 2014

Cited by 74 | Viewed by 31518

Abstract

BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed [...] Read more.

BPC 157, a pentadecapeptide derived from human gastric juice, has been demonstrated to promote the healing of different tissues, including skin, muscle, bone, ligament and tendon in many animal studies. However, the underlying mechanism has not been fully clarified. The present study aimed to explore the effect of BPC 157 on tendon fibroblasts isolated from Achilles tendon of male Sprague-Dawley rat. From the result of cDNA microarray analysis, growth hormone receptor was revealed as one of the most abundantly up-regulated genes in tendon fibroblasts by BPC 157. BPC 157 dose- and time-dependently increased the expression of growth hormone receptor in tendon fibroblasts at both the mRNA and protein levels as measured by RT/real-time PCR and Western blot, respectively. The addition of growth hormone to BPC 157-treated tendon fibroblasts dose- and time-dependently increased the cell proliferation as determined by MTT assay and PCNA expression by RT/real-time PCR. Janus kinase 2, the downstream signal pathway of growth hormone receptor, was activated time-dependently by stimulating the BPC 157-treated tendon fibroblasts with growth hormone. In conclusion, the BPC 157-induced increase of growth hormone receptor in tendon fibroblasts may potentiate the proliferation-promoting effect of growth hormone and contribute to the healing of tendon. Full article

(This article belongs to the Section Medicinal Chemistry)

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BPC 157 increased the expression of growth hormone receptor in tendon fibroblasts. Tendon fibroblasts at 50%–60% confluency were treated with BPC 157 at concentrations of 0, 0.1, 0.25, 0.5 μg/mL for 24 h (A and C) or 0.5 μg/mL for one to three days (B and D). The mRNA (A and B) and protein (C and D) expressions of growth hormone receptor were measured by RT/real-time PCR and Western blot analysis, respectively. Experiments were done in triplicate. Full article ">Figure 2
Growth hormone increased the cell number of BPC 157-treated tendon fibroblasts. Tendon fibroblasts at 50%–60% confluency were pretreated with BPC 157 at concentrations of 0, 0.1, 0.25, 0.5 μg/mL for 24 h (A) or 0.5 μg/mL for one to three days (B). After BPC 157 pretreatment, 0.1 μg/mL growth hormone was added for another 24 h and then MTT assay was performed. Experiments were done in triplicate. The “★” would be applied if there is statistically significant. Full article ">Figure 3
Growth hormone increased the PCNA gene expression in BPC 157-treated tendon fibroblasts. Tendon fibroblasts at 50%–60% confluency were pretreated with BPC 157 at concentrations of 0, 0.1, 0.25, 0.5 μg/mL for 24 h (A) or 0.5 μg/mL for one to three days (B). After BPC 157 pretreatment, 0.1 μg/mL growth hormone was added for another 24 h and then the PCNA gene expression was analyzed by RT/real-time PCR. Experiments were done in triplicate. The “★” would be applied if there is statistically significant. Full article ">Figure 4
Growth hormone activated more JAK2 proteins in BPC 157-treated tendon fibroblasts. Tendon fibroblasts at 50%–60% confluency were pretreated with BPC 157 at concentration of 0.5 μg/mL for one to three days. After BPC 157 pretreatment, 0.1 μg/mL growth hormone was added for another 24 h and then total JAK2 (which was not shown) and activation of JAK2 which was determined by the level of phosphorylated JAK2 were detected by Western blot analysis (A). Experiments were done in triplicate. The levels of phosphorylated JAK2 were calculated by direct densitomeric analysis of the blot (B). The “★” would be applied if there is statistically significant. Full article ">

2267 KiB

Open AccessArticle

Synthesis and Biological Evaluation of New Pleuromutilin Derivatives as Antibacterial Agents

by Ruo-Feng Shang, Guan-Hua Wang, Xi-Ming Xu, Si-Jie Liu, Chao Zhang, Yun-Peng Yi, Jian-Ping Liang and Yu Liu

Molecules 2014, 19(11), 19050-19065; https://doi.org/10.3390/molecules191119050 - 19 Nov 2014

Cited by 33 | Viewed by 7789

Abstract

Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus [...] Read more.

Several pleuromutilin derivatives possessing thiadiazole moieties were synthesized via acylation reactions under mild conditions. The in vitro antibacterial activities of the derivatives against methicillin-resistant S. aureus, methicillin-resistant S. epidermidis, S. aureus, S. epidermidis, E. coli, and B. cereus were tested by the agar dilution method and Oxford cup assay. All the screened compounds displayed potent activity. Compound 6d was the most active antibacterial agent because of its lowest MIC value and largest inhibition zone. Docking experiments were performed to understand the possible mode of the interactions between the derivatives and 50S ribosomal subunit. Moreover, the absorption, distribution, metabolism, excretion and toxicity properties of the synthesized compounds were analyzed after prediction using the Advanced Chemistry Development/Percepta Platform available online. Full article

(This article belongs to the Section Medicinal Chemistry)

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Full article ">Figure 1
Structural formulas of pleuromutilin, tiamulin, valnemulin, retapamulin, BC-3781, BC-3205 and BC-7013. Full article ">Figure 2
Superimposition of native ligand, tiamulin (colored by red) and the best conformations of 5a (green), 5b (blue), 5c (yellow), 6a (magenta), 6b (cyan), 6c (orange) and 6d (wheat) docked to the binding pocket of ribosome (1XBP). Full article ">Figure 3
Docking modes of the synthesized compounds into 1XBP. (A) 5a (green), 5b (magenta) and 5c (yellow); (B) 6a (green) and 6b (magenta) to 1XBP; (C) 6c (green) and 6d (magenta). Important residues are drawn in stick and different color. Hydrogen bonds and cation–π interaction are showed as dashed red lines. Full article ">Figure 4
Correlation between binding free energy (ΔGb, kcal/mol) and antibacterial activity (zone of inhibition; mm) against E. coli. for scereened compounds with 320 μg/mL (A) and 160 μg/mL (B). Full article ">Figure 5
Synthesis of compounds 5a–c and 6a–d. Full article ">

2948 KiB

Open AccessArticle

Antioxidant Mechanism of Rutin on Hypoxia-Induced Pulmonary Arterial Cell Proliferation

by Qian Li, Yanli Qiu, Min Mao, Jinying Lv, Lixin Zhang, Shuzhen Li, Xia Li and Xiaodong Zheng

Molecules 2014, 19(11), 19036-19049; https://doi.org/10.3390/molecules191119036 - 18 Nov 2014

Cited by 40 | Viewed by 10533

Abstract

Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, [...] Read more.

Reactive oxygen species (ROS) are involved in the pathologic process of pulmonary arterial hypertension as either mediators or inducers. Rutin is a type of flavonoid which exhibits significant scavenging properties on oxygen radicals both in vitro and in vivo. In this study, we proposed that rutin attenuated hypoxia-induced pulmonary artery smooth muscle cell (PASMC) proliferation by scavenging ROS. Immunofluorescence data showed that rutin decreased the production of ROS, which was mainly generated through mitochondria and NADPH oxidase 4 (Nox4) in pulmonary artery endothelial cells (PAECs). Western blot results provided further evidence on rutin increasing expression of Nox4 and hypoxia-inducible factor-1α (HIF-1α). Moreover, cell cycle analysis by flow cytometry indicated that proliferation of PASMCs triggered by hypoxia was also repressed by rutin. However, N-acetyl-L-cysteine (NAC), a scavenger of ROS, abolished or diminished the capability of rutin in repressing hypoxia-induced cell proliferation. These data suggest that rutin shows a potential benefit against the development of hypoxic pulmonary arterial hypertension by inhibiting ROS, subsequently preventing hypoxia-induced PASMC proliferation. Full article

(This article belongs to the Section Natural Products Chemistry)

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Immunofluorescence staining using CM-H2DCFDA or mitosox to evaluate the production of reactive oxygen species (ROS) in pulmonary artery endothelial cells (PAECs) and mitochondria. (A) Chemical structure of rutin. (B) The increased production of ROS in cells (Green) and mitochondria (Red) induced by hypoxia was reduced when treated with rutin. (C) Cells were pretreated with APO (apocynin, NADPH oxidases inhibitor), RE (rotenone, mitochondria inhibitor), showed the reverse effect of rutin on pulmonary endothelial cells, respectively. ROS was assessed by a laser-scanning confocal microscope after treatment by CM-H2DCFDA for the detection of the whole cells (Green) and mitosox (Red) for the detection of mitochondria respectively. Scale bars were 100 μm. Nor indicates normoxia, Hyp indicates hypoxia, Ru: rutin. Full article ">Figure 2
The regulative effect of rutin on the expression of NADPH oxidase 4 (Nox4) under hypoxia was evaluated by Western Blot. Under hypoxia, the activity of Nox4 was decreased when treated with rutin, or N-acetyl-l-cysteine (NAC) (5 μmol/L) suppressed the effect of rutin evidently in PAECs (A) and pulmonary arterial smooth muscle cells (PASMCs). (B) All of the values were denoted as mean ± SD; * p < 0.05, versus normal; # p < 0.05, versus Hyp. Nor indicates normoxia, Hyp indicates hypoxia. Full article ">Figure 3
Rutin blocked PAECs migration and PASMCs proliferation under hypoxia by regulating ROS. (A) The effect of hypoxia (8 h) on cell migration was blocked by rutin (n = 3), which was attenuated by NAC. Scale bars are 100 μm. (B) Cell viability was measured by MTT, the results were consistent with scratch-wound assay, rutin abolished hypoxia-increasing PASMCs viability, which was blocked with NAC. (C) NAC (ROS scavenger, 5 μmol/L) increased 5-bromodeoxyuridine incorporation compared with the rutin group under hypoxia. All of the values were denoted as mean ± SD; * p < 0.05, ** p < 0.01, versus normal; # p < 0.05, ## p < 0.01 versus Hyp, n = 3. Nor indicates normoxia, Hyp indicates hypoxia. Full article ">Figure 4
Rutin reversed the increased expression of proliferating cell nuclear antigen (PCNA) during hypoxia. Evaluation of the expression of PCNA in PAECs (A) and PASMCs (B) by Western Blot. The abnormal increased activity of PCNA induced by hypoxia was alleviated by rutin. All of the values were denoted as mean ± SD; * p < 0.05, versus normal; ## p < 0.01 versus Hyp, n = 3. Nor indicates normoxia, Hyp indicates hypoxia. Full article ">Figure 5
The influence of rutin on the activity of PASMCs was detected with flow cytometry and the expression of α-tubulin was recorded with immunohistochemistry. (A) Hypoxia promoted PASMCs cycle progression and increased the cell number in S plus G2/M phases, which was suppressed in the presence of rutin. The effect of rutin on hypoxia-induced enhanced cycle progression was eliminated with scavenged ROS by NAC. (B) The expression of α-tubulin in PASMCs was upregulated under hypoxia which was blocked by rutin, and the role of rutin was eliminated in the presence of NAC (ROS scavenger, 5 μmol/L). Scale bars were 100 μm. All of the values were denoted as mean ± SD; ** p < 0.01, versus normal; ## p < 0.01, versus Hyp. n = 3. Nor indicates normoxia, Hyp indicates hypoxia. Full article ">Figure 6
Rutin affected the expression of hypoxia-inducible factor-1α (HIF-1α) when exposed under hypoxia. The upregulated expression of HIF-1α of PAECs (A) and PASMCs (B) induced by hypoxia was repressed by rutin, and the effect of rutin on hypoxia-induced overexpression of HIF-1α was alleviated by NAC. All of the values were denoted as mean ± SD; ** p < 0.01, versus normal; ## p < 0.01versus Hyp. n = 3. Nor indicates normoxia, Hyp indicates hypoxia. Full article ">

302 KiB

Open AccessArticle

Design, Synthesis, and Biological Evaluation of Artemisinin-Indoloquinoline Hybrids as Potent Antiproliferative Agents

by Li Wang, Marta Świtalska, Ning Wang, Zhen-Jun Du, Yuta Fukumoto, Nguyen Kim Diep, Ryo Kiguchi, Junzo Nokami, Joanna Wietrzyk and Tsutomu Inokuchi

Molecules 2014, 19(11), 19021-19035; https://doi.org/10.3390/molecules191119021 - 18 Nov 2014

Cited by 24 | Viewed by 10021

Abstract

A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a–7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in [...] Read more.

A series of artemisinin-indoloquinoline hybrids were designed and synthesized in an attempt to develop potent and selective anti-tumor agents. Compounds 7a–7f, 8 and 9 were prepared and characterized. Their antiproliferative activities against MV4-11, HCT-116, A549, and BALB/3T3 cell lines in vitro were tested. Nearly all of the tested compounds (7–9, except for compounds 7d and 7e against HCT-116) showed an increased antitumor activity against HCT-116 and A549 cell lines when compared to the dihydroartemisinin control. Especially for the artemisinin-indoloquinoline hybrid 8, with an 11-aminopropylamino-10H-indolo[3,2-b]quinoline substituent, the antiproliferative activity against the A549 cell line had improved more than ten times. The IC₅₀ value of hybrid 8 against A549 cell lines was decreased to 1.328 ± 0.586 μM, while dihydroartemisin showed IC₅₀ value of >20 µM in the same cell line. Thus, these results have proven that the strategy of introducing a planar basic fused aromatic moiety, such as the indoloquinoline skeleton, could improve the antiproliferative activity and selectivity towards cancer cell lines. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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259 KiB

Open AccessArticle

Essential Oil of Eucalyptus Gunnii Hook. As a Novel Source of Antioxidant, Antimutagenic and Antibacterial Agents

by Dušan Bugarin, Slavenko Grbović, Dejan Orčič, Dragana Mitić-Ćulafić, Jelena Knežević-Vukčević and Neda Mimica-Dukić

Molecules 2014, 19(11), 19007-19020; https://doi.org/10.3390/molecules191119007 - 18 Nov 2014

Cited by 19 | Viewed by 8097

Abstract

The present study describes radical scavenging capacity (RSC), antimutagenic and antibacterial properties of the essential oil (EO) of the leaves of Eucalyptus gunnii Hook. (Southern Montenegro). Chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). In oil, 1,8-cineole (67.8%) and [...] Read more.

The present study describes radical scavenging capacity (RSC), antimutagenic and antibacterial properties of the essential oil (EO) of the leaves of Eucalyptus gunnii Hook. (Southern Montenegro). Chemical composition was evaluated by gas chromatography-mass spectrometry (GC-MS). In oil, 1,8-cineole (67.8%) and α-pinene (14.12%) were the major compounds comprising almost 82% of total EO. EO exhibited moderate DPPH (2,2-diphenyl-1-picrylhydrazyl) scavenging activity, with IC₅₀ value of 7.19 µL/mL. The antimutagenic properties were assayed against the spontaneous and t-BOOH-induced mutagenesis in Escherichia coli IC202 oxyR mutant strain, deficient in removing radical oxygen species (ROS). Reduction of the spontaneous mutagenesis in the presence of E. gunnii EO was only slight, up to 12% at the highest concentration tested. However, when the oxidative mutagen was used, EO displayed more significant reduction of mutagenesis (maximum 23%) in a concentration dependent manner. Antibacterial activity was tested against the selected strains from ATTC and NCIB collections: Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Escherichia coli, Bacillus subtilis, Micrococcus flavus, Klebsiella pneumoniae, and the two Escherichia coli strains from our laboratory collection (SY252 and IB112) using both the disk-diffusion and MIC assays. The greatest sensitivity was shown by M. flavus, K. pneumoniae and E. coli lpcA (MIC = 0.83 mg/mL), while the highest resistance was shown by E. coli (ATTC 25922) and S. epidermidis. This study represents the first report on chemical composition and biological activity of the Eucalyptus gunnii in the South Balkan region and beyond. Full article

(This article belongs to the Collection Bioactive Compounds)

874 KiB

Open AccessArticle

Study on the Cytotoxic Activity of Drimane Sesquiterpenes and Nordrimane Compounds against Cancer Cell Lines

by Ivan Montenegro, Giacomo Tomasoni, Claudia Bosio, Natalia Quiñones, Alejandro Madrid, Hector Carrasco, Andres Olea, Rolando Martinez, Mauricio Cuellar and Joan Villena

Molecules 2014, 19(11), 18993-19006; https://doi.org/10.3390/molecules191118993 - 18 Nov 2014

Cited by 30 | Viewed by 8127

Abstract

Twelve drimanes, including polygodial (1), isopolygodial (2), drimenol (3), confertifolin (4), and isodrimenin (5), were obtained from natural sources. Semi-synthetic derivatives 6–12 were obtained from 1 and 2, and cytotoxic [...] Read more.

Twelve drimanes, including polygodial (1), isopolygodial (2), drimenol (3), confertifolin (4), and isodrimenin (5), were obtained from natural sources. Semi-synthetic derivatives 6–12 were obtained from 1 and 2, and cytotoxic activity was evaluated in vitro against cancer cell lines (HT-29, MDA-MB231, DHF, MCF-7, PC-3, DU-145, and CoN). IC₅₀ values were determined at concentrations of 12.5–100 µM of each compound for 72 h. In addition, it was found that polygodial (1), 8, and 12 induced changes in mitochondrial membrane permeability in CoN, MCF-7, and PC-3 cells. Full article

(This article belongs to the Collection Efficient Pharmaceutical and Chemical Approaches for Anticancer Therapy: Design, Preliminary Evaluations, and Further Developments)

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Figure 1
Structure of natural drimanes from bark of the D. winteri. Full article ">Figure 2
Bottom: 1H-NMR spectrum of compound 12. Top: 1D 1H NOESY experiment (selnogp pulse program from Bruker Library) showing the main long-range interactions between CH3-12 and H-9, H-9 and CH3-15. Full article ">Figure 3
Effect of tested compounds on the morphologies of CoN, MCF-7 and PC-3 cells. Images obtained with an inverted phase contrast microscope (200×) after 24 h exposure of the cells to 50 μM of compounds 1, 8, and 12. (1% ethanol) and similar to control positive (5-fluorouracil, 5-FU). Full article ">Figure 4
Effect of compounds 1, 8 and 12 on chromatin condensation and fragmentation. CoN, MCF-7 and PC-3 cells treated with one of the compounds were stained with Hoechst 33342 (200×). Representative photographs presented here show nuclear morphologic changes observed by fluorescent microscopy of the treated cells. As positive control, 5-fluorouracyl (25 μM) was used. Full article ">Figure 5
Effect of compounds 1, 8, and 12 on caspase-3 activity of MCF-7 (black), CoN (white) and PC-3 (grey) cells. Cells were exposed to compounds at 50 μM for different times. Values are mean ± S.D. (n = 3). All data are reported as the percentage change in comparison with the vehicle-treated cells (1% ethanol), which were arbitrarily assigned 100%. # p < 0.05, significantly different from the vehicle-treated cells (1% ethanol in medium, that is, compound concentration = 0) and * p < 0.001, significantly different from the vehicle-treated cells. Full article ">Figure 6
Modifications performed on 1 to obtain compounds 6–8. Full article ">Figure 7
Modifications performed on 3 to obtain compounds 9–12. Full article ">

584 KiB

Open AccessArticle

Classification of Frankfurters by FT-Raman Spectroscopy and Chemometric Methods

by Náira Da Silva Campos, Kamila Sá Oliveira, Mariana Ramos Almeida, Rodrigo Stephani and Luiz Fernando Cappa De Oliveira

Molecules 2014, 19(11), 18980-18992; https://doi.org/10.3390/molecules191118980 - 18 Nov 2014

Cited by 20 | Viewed by 6475

Abstract

Frankfurters are widely consumed all over the world, and the production requires a wide range of meat and non-meat ingredients. Due to these characteristics, frankfurters are products that can be easily adulterated with lower value meats, and the presence of undeclared species. Adulterations [...] Read more.

Frankfurters are widely consumed all over the world, and the production requires a wide range of meat and non-meat ingredients. Due to these characteristics, frankfurters are products that can be easily adulterated with lower value meats, and the presence of undeclared species. Adulterations are often still difficult to detect, due the fact that the adulterant components are usually very similar to the authentic product. In this work, FT-Raman spectroscopy was employed as a rapid technique for assessing the quality of frankfurters. Based on information provided by the Raman spectra, a multivariate classification model was developed to identify the frankfurter type. The aim was to study three types of frankfurters (chicken, turkey and mixed meat) according to their Raman spectra, based on the fatty vibrational bands. Classification model was built using partial least square discriminant analysis (PLS-DA) and the performance model was evaluated in terms of sensitivity, specificity, accuracy, efficiency and Matthews’s correlation coefficient. The PLS-DA models give sensitivity and specificity values on the test set in the ranges of 88%–100%, showing good performance of the classification models. The work shows the Raman spectroscopy with chemometric tools can be used as an analytical tool in quality control of frankfurters. Full article

(This article belongs to the Special Issue Advances of Vibrational Spectroscopic Technologies in Life Sciences)

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399 KiB

Open AccessArticle

The Diterpenes Ovoideal A–G from Tirpitzia ovoidea

by Dan Su, Xue-Yan Yang, Xu Feng, Ming-Ying Shang and Shao-Qing Cai

Molecules 2014, 19(11), 18966-18979; https://doi.org/10.3390/molecules191118966 - 18 Nov 2014

Cited by 13 | Viewed by 6473

Abstract

Seven new diterpenes, named ovoideal A (1), B (2), C (3), D (4), E (5), F (6) and G (7), have been isolated along with eleven known diterpenes 8 [...] Read more.

Seven new diterpenes, named ovoideal A (1), B (2), C (3), D (4), E (5), F (6) and G (7), have been isolated along with eleven known diterpenes 8–18 from the petroleum ether soluble fraction of an ethanol extract of the aerial parts of Tirpitzia ovoidea. The structures of the new compounds were elucidated primarily by 1D and 2D NMR spectroscopy, as well as by the HR-ESI-MS spectrometry. All compounds were isolated from the Linaceae family for the first time. The in vitro cytotoxic activity of compounds 1, 3–5, 8–18 was evaluated against the Hela, HepG2 and K562 cell lines. Among them, compounds 3, 9, 11, 12, 13, 14, 15, 17, 18 showed moderate inhibitory activities. Full article

(This article belongs to the Section Medicinal Chemistry)

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256 KiB

Open AccessArticle

TOMBU and COMBU as Novel Uronium-Type Peptide Coupling Reagents Derived from Oxyma-B

by Yahya E. Jad, Sherine N. Khattab, Beatriz G. De la Torre, Thavendran Govender, Hendrik G. Kruger, Ayman El-Faham and Fernando Albericio

Molecules 2014, 19(11), 18953-18965; https://doi.org/10.3390/molecules191118953 - 18 Nov 2014

Cited by 11 | Viewed by 15187

Abstract

Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis, [...] Read more.

Here we describe two novel uronium salts, TOMBU and COMBU, derived from the recently described Oxyma-B for use in peptide bond synthesis. These coupling reagents are more stable than COMU in DMF. Furthermore, using various peptide synthetic models in solution and solid-phase synthesis, we reveal that they show better performance than HBTU in terms of preserving chiral integrity and coupling yields, but slightly worse performance than COMU. Full article

(This article belongs to the Section Organic Chemistry)

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1013 KiB

Open AccessArticle

Monoamine Oxidase Inhibitory Constituents of Propolis: Kinetics and Mechanism of Inhibition of Recombinant Human MAO-A and MAO-B

by Narayan D. Chaurasiya, Mohamed A. Ibrahim, Ilias Muhammad, Larry A. Walker and Babu L. Tekwani

Molecules 2014, 19(11), 18936-18952; https://doi.org/10.3390/molecules191118936 - 18 Nov 2014

Cited by 55 | Viewed by 14550

Abstract

Propolis is the resinous material that bees gather from leaf buds, flowers and vegetables. Propolis extracts contain constituents with a broad spectra of pharmacological properties and are important ingredients of popular dietary supplements. Propolis extracts were evaluated in vitro for inhibition of recombinant [...] Read more.

Propolis is the resinous material that bees gather from leaf buds, flowers and vegetables. Propolis extracts contain constituents with a broad spectra of pharmacological properties and are important ingredients of popular dietary supplements. Propolis extracts were evaluated in vitro for inhibition of recombinant human monoamine oxidase (MAO)-A and MAO-B. The dichloromethane extract of propolis showed potent inhibition of human MAO-A and MAO-B. Further fractionation identified the most active fractions as rich in flavonoids. Galangin and apigenin were identified as the principal MAO-inhibitory constituents. Inhibition of MAO-A by galangin was about 36 times more selective than MAO-B, while apigenin selectivity for MAO-A vs. MAO-B was about 1.7 fold. Apigenin inhibited MAO-B significantly more potently than galangin. Galangin and apigenin were further evaluated for kinetic characteristics and the mechanism for the enzymes’ inhibition. Binding of galangin and apigenin with MAO-A and -B was not time-dependent and was reversible, as suggested by enzyme-inhibitor binding and dissociation-dialysis assay. The inhibition kinetics studies suggested that galangin and apigenin inhibited MAO-A and -B by a competitive mechanism. Presence of prominent MAO inhibitory constituents in propolis products suggests their potential for eliciting pharmacological effects that might be useful in depression or other neurological disorders. The results may also have important implications in drug-dietary supplement interactions. Full article

(This article belongs to the Section Natural Products Chemistry)

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Full article ">Figure 1
Structure of galangin (1) and apigenin (2). Full article ">Figure 2
Kinetic characteristics of inhibition of recombinant human MAO-A with [A] galangin and [B] apigenin; V = nmoles/min/mg protein and S = substrate kynuramine concentration (μM). Full article ">Figure 3
Kinetic characteristics of inhibition of recombinant human MAO-B with [A] galangin and [B] apigenin; V = nmoles/min/mg protein and S = substrate kynuramine concentration (μM). Full article ">Figure 4
Time-dependent inhibition of recombinant human MAO-A by galangin (0.25 μM), apigenin (1.2 μM) and clorgyline (7.5 nM). The remaining activity was expressed as % of activity. Each point represents mean ± S.D. of triplicate values. Full article ">Figure 5
Time-dependent inhibition of recombinant human MAO-B by galangin (14.0 μM), apigenin (4.0 μM) and l-deprenyl (0.050 μM). The remaining activity was expressed as % of activity. Each point represents mean ± S.D. of triplicate values. Full article ">Figure 6
Analysis of nature of binding of galangin and apigenin with recombinant human MAO- A by recovery of catalytic activity of the enzyme after dialysis dissociation. Each bar shows mean ± S.D. of triplicate values. Full article ">Figure 7
Analysis of nature of binding of galangin and apigenin with recombinant human MAO- B by recovery of catalytic activity of the enzyme after dialysis dissociation. Each bar shows mean ± S.D. of triplicate values. Full article ">

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Open AccessArticle

Method Development and Validation for Pharmacokinetic and Tissue Distributions of Ellagic Acid Using Ultrahigh Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS)

by Linlin Yan, Peipei Yin, Chao Ma and Yujun Liu

Molecules 2014, 19(11), 18923-18935; https://doi.org/10.3390/molecules191118923 - 18 Nov 2014

Cited by 51 | Viewed by 10917

Abstract

Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A [...] Read more.

Ellagic acid is a dietary polyphenol found in numerous fruits and vegetables, possessing several health benefits such as antioxidant, anticancer and anti-atherosclerotic biological properties. The purpose of this study was to explore the pharmacokinetics and tissue distribution of ellagic acid in rats. A simple, rapid, sensitive and specific liquid chromatography–tandem mass spectrometry method to determine the ellagic acid in plasma and tissue samples was developed and validated. The separation was achieved using reversed-phase ultra-performance liquid chromatography (UPLC), and the mass spectrometric detection was achieved using heated electrospray ionization (negative mode) and multiple ion monitoring (m/z 301/229). A sample cleanup with a solid phase extraction (SPE) step prior to the UPLC-MS/MS analysis was also developed. The SPE and UPLC-MS/MS method established here was successfully applied to reveal the pharmacokinetic profiles and tissue distribution of ellagic acid. After oral administration dosing at 50 mg/kg, plasma levels of ellagic acid peaked at about 0.5 h, with C_max value of 93.6 ng/mL, and the results showed that the ellagic acid was poorly absorbed after oral administration. The pharmacokinetic profile of ellagic acid fitted to a two-compartment model with t_1/2α 0.25 h and t_1/2β 6.86 h, respectively. Following oral administration, ellagic acid was detected in all examined tissues including kidney, liver, heart, lung and brain et al., and the highest levels were found in kidney and liver. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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261 KiB

Open AccessArticle

Preparation of Rotenone Derivatives and in Vitro Analysis of Their Antimalarial, Antileishmanial and Selective Cytotoxic Activities

by Yulieth Upegui, Juan F. Gil, Wiston Quiñones, Fernando Torres, Gustavo Escobar, Sara M. Robledo and Fernando Echeverri

Molecules 2014, 19(11), 18911-18922; https://doi.org/10.3390/molecules191118911 - 18 Nov 2014

Cited by 14 | Viewed by 7872

Abstract

Six derivatives of the known biopesticide rotenone were prepared by several chemical transformations. Rotenone and its derivatives showed differential in vitro antiparasitic activity and selective cytotoxicity. In general, compounds were more active against Plasmodium falciparum than Leishmania panamensis. Rotenone had an EC [...] Read more.

Six derivatives of the known biopesticide rotenone were prepared by several chemical transformations. Rotenone and its derivatives showed differential in vitro antiparasitic activity and selective cytotoxicity. In general, compounds were more active against Plasmodium falciparum than Leishmania panamensis. Rotenone had an EC₅₀ of 19.0 µM against P. falciparum, and 127.2 µM against L. panamensis. Although chemical transformation does not improve its biological profile against P. falciparum, three of its derivatives showed a significant level of action within an adequate range of activity with EC₅₀values < 50.0 µM. This antiplasmodial activity was not due to red blood cell hemolysis, since LC₅₀ was >>400 µM. On the other hand, all derivatives displayed a non-specific cytotoxicity on several cell lines and primary human cell cultures. Full article

(This article belongs to the Collection Natural Products as Leads or Drugs against Neglected Tropical Diseases)

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301 KiB

Open AccessArticle

Synthesis, Characterization and Antimicrobial Evaluation of Some New Schiff, Mannich and Acetylenic Mannich Bases Incorporating a 1,2,4-Triazole Nucleus

by Mohamed R. Aouad

Molecules 2014, 19(11), 18897-18910; https://doi.org/10.3390/molecules191118897 - 18 Nov 2014

Cited by 26 | Viewed by 7429

Abstract

A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluoro-phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl₂ furnished [...] Read more.

A series of Schiff and Mannich bases derived from 4-amino-5-(3-fluoro-phenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione were synthesized. The alkylation of 4-phenyl-5-(3-fluorophenyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione with propargyl bromide afforded the corresponding thiopropargylated derivative which upon treatment with the appropriate secondary amines in the presence of CuCl₂ furnished the desired acetylenic Mannich bases. The synthesized compounds were characterized on the basis of their spectral (IR, ¹H- and ¹³C-NMR) data and evaluated for their biological activities. Some of the compounds were found to exhibit significant antimicrobial activity. Full article

(This article belongs to the Section Organic Chemistry)

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427 KiB

Open AccessArticle

Profiling the Metabolism of Astragaloside IV by Ultra Performance Liquid Chromatography Coupled with Quadrupole/Time-of-Flight Mass Spectrometry

by Xu-Dong Cheng and Ming-Gang Wei

Molecules 2014, 19(11), 18881-18896; https://doi.org/10.3390/molecules191118881 - 17 Nov 2014

Cited by 23 | Viewed by 8110

Abstract

Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological [...] Read more.

Astragaloside IV is a compound isolated from the Traditional Chinese Medicine Astragalus membranaceus, that has been reported to have bioactivities against cardiovascular disease and kidney disease. There is limited information on the metabolism of astragaloside IV, which impedes comprehension of its biological actions and pharmacology. In the present study, an ultra-performance liquid chromatography coupled with quadrupole/time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)-based approach was developed to profile the metabolites of astragaloside IV in rat plasma, bile, urine and feces samples. Twenty-two major metabolites were detected. The major components found in plasma, bile, urine and feces included the parent chemical and phases I and II metabolites. The major metabolic reactions of astragaloside IV were hydrolysis, glucuronidation, sulfation and dehydrogenation. These results will help to improve understanding the metabolism and reveal the biotransformation profiling of astragaloside IV in vivo. The metabolic information obtained from our study will guide studies into the pharmacological activity and clinical safety of astragaloside IV. Full article

(This article belongs to the Collection Phytochemicals: Biosynthesis, Metabolism and Biological Activities)

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1430 KiB

Open AccessReview

A Review of Recent Research Progress on the Astragalus Genus

by Xiaoxia Li, Lu Qu, Yongzhe Dong, Lifeng Han, Erwei Liu, Shiming Fang, Yi Zhang and Tao Wang

Molecules 2014, 19(11), 18850-18880; https://doi.org/10.3390/molecules191118850 - 17 Nov 2014

Cited by 263 | Viewed by 26011

Abstract

Astragalus L., is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. and its processed products are listed in the China Pharmacopeia for “qi deficiency” syndrome [...] Read more.

Astragalus L., is one of the largest genuses of flowering plants in the Leguminosae family. Roots of A. membranaceus Bge. var. mongholicus (Bge.) Hsiao, A. membranaceus (Fisch.) Bge. and its processed products are listed in the China Pharmacopeia for “qi deficiency” syndrome treatment. However, more and more researches on other species of Astragalus have been conducted recently. We summarize the recent researches of Astragalus species in phytochemistry and pharmacology. More than 200 constituents, including saponins and flavonoids, obtained from 46 species of Astragalus genus were collected for this article. In pharmacological studies, crude extracts of Astragalus, as well as isolated constituents showed anti-inflammatory, immunostimulant, antioxidative, anti-cancer, antidiabetic, cardioprotective, hepatoprotective, and antiviral activities. The goal of this article is to provide an overview of chemical and pharmacological studies on the Astragalus species over the last 10 years, which could be of value to new drug or food supplement research and development. Full article

(This article belongs to the Section Natural Products Chemistry)

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363 KiB

Open AccessArticle

Kinetics of Glycoxidation of Bovine Serum Albumin by Glucose, Fructose and Ribose and Its Prevention by Food Components

by Izabela Sadowska-Bartosz, Sabina Galiniak and Grzegorz Bartosz

Molecules 2014, 19(11), 18828-18849; https://doi.org/10.3390/molecules191118828 - 17 Nov 2014

Cited by 83 | Viewed by 9173

Abstract

The aim of this study was to compare the kinetics of the glycoxidation of bovine serum albumin (BSA) as a model protein by three sugars: glucose, fructose and ribose, using fluorometric measurements of the content of advanced glycation end products (AGEs), protein-bound fructosamine, [...] Read more.

The aim of this study was to compare the kinetics of the glycoxidation of bovine serum albumin (BSA) as a model protein by three sugars: glucose, fructose and ribose, using fluorometric measurements of the content of advanced glycation end products (AGEs), protein-bound fructosamine, dityrosine, N'-formylkynurenine, kynurenine, tryptophan, the content of advanced oxidation protein products (AOPP), protein carbonyl groups, as well as thiol groups. Moreover, the levels of glycoalbumin and AGEs were determined by using an enzyme-linked immunosorbent assay. Based on the kinetic results, the optimal incubation time for studies of the modification of the glycoxidation rate by additives was chosen, and the effects of 25 compounds of natural origin on the glycoxidation of BSA induced by various sugars were examined. The same compounds were found to have different effects on glycoxidation induced by various sugars, which suggests caution in extrapolation from experiments based on one sugar to other sugars. From among the compounds tested, the most effective inhibitors of glycoxidation were: polyphenols, pyridoxine and 1-cyano-4-hydroxycinnamic acid. Full article

(This article belongs to the Section Medicinal Chemistry)

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Figure 1
The time course of the glycoxidation of BSA incubated at 37 °C for 14 days with 0.05, 0.1 and 0.5 M glucose (Glu), fructose (Fru) and ribose (Rib): AGE fluorescence (A,B); fructosamine content (C); dityrosine content (D,E); N'-formylkynurenine content (F,G); N-formylkynurenine content (H,I); advanced oxidation protein products (AOPP) content (J); tryptophan fluorescence; (K) and sulfhydryl group content (L). Full article ">Figure 1 Cont.
The time course of the glycoxidation of BSA incubated at 37 °C for 14 days with 0.05, 0.1 and 0.5 M glucose (Glu), fructose (Fru) and ribose (Rib): AGE fluorescence (A,B); fructosamine content (C); dityrosine content (D,E); N'-formylkynurenine content (F,G); N-formylkynurenine content (H,I); advanced oxidation protein products (AOPP) content (J); tryptophan fluorescence; (K) and sulfhydryl group content (L). Full article ">Figure 1 Cont.
The time course of the glycoxidation of BSA incubated at 37 °C for 14 days with 0.05, 0.1 and 0.5 M glucose (Glu), fructose (Fru) and ribose (Rib): AGE fluorescence (A,B); fructosamine content (C); dityrosine content (D,E); N'-formylkynurenine content (F,G); N-formylkynurenine content (H,I); advanced oxidation protein products (AOPP) content (J); tryptophan fluorescence; (K) and sulfhydryl group content (L). Full article ">

254 KiB

Open AccessReview

Banana Lectin: A Brief Review

by Senjam Sunil Singh, Sanjenbam Kunjeshwori Devi and Tzi Bun Ng

Molecules 2014, 19(11), 18817-18827; https://doi.org/10.3390/molecules191118817 - 17 Nov 2014

Cited by 33 | Viewed by 13194

Abstract

Lectins are a group of proteins of non-immune origin that recognize and bind to carbohydrates without modifying them. Banana is the common name for both herbaceous plants of the genus Musa and for the fruit they produce. They are indeed a promising source [...] Read more.

Lectins are a group of proteins of non-immune origin that recognize and bind to carbohydrates without modifying them. Banana is the common name for both herbaceous plants of the genus Musa and for the fruit they produce. They are indeed a promising source for many medicinal applications. Banana lectins have the potential for inhibiting HIV-1 reverse transcriptase activity, suppressing cancer cell proliferation and stimulating macrophage activities. Nevertheless, compared to other plant lectins, there is relatively little information in the literature on banana lectins, particularly with respect to their structure and biological functions. Herein we focus our review on the structure, functions and exploitable properties of banana lectins. Full article

(This article belongs to the Special Issue Lectins)

734 KiB

Open AccessReview

Cannabinoids: New Promising Agents in the Treatment of Neurological Diseases

by Sabrina Giacoppo, Giuseppe Mandolino, Maria Galuppo, Placido Bramanti and Emanuela Mazzon

Molecules 2014, 19(11), 18781-18816; https://doi.org/10.3390/molecules191118781 - 17 Nov 2014

Cited by 61 | Viewed by 28267

Abstract

Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds [...] Read more.

Nowadays, Cannabis sativa is considered the most extensively used narcotic. Nevertheless, this fame obscures its traditional employ in native medicine of South Africa, South America, Turkey, Egypt and in many regions of Asia as a therapeutic drug. In fact, the use of compounds containing Cannabis and their introduction in clinical practice is still controversial and strongly limited by unavoidable psychotropic effects. So, overcoming these adverse effects represents the main open question on the utilization of cannabinoids as new drugs for treatment of several pathologies. To date, therapeutic use of cannabinoid extracts is prescribed in patients with glaucoma, in the control of chemotherapy-related vomiting and nausea, for appetite stimulation in patients with anorexia-cachexia syndrome by HIV, and for the treatment of multiple sclerosis symptoms. Recently, researcher efforts are aimed to employ the therapeutic potentials of Cannabis sativa in the modulation of cannabinoid receptor activity within the central nervous system, particularly for the treatment of neurodegenerative diseases, as well as psychiatric and non-psychiatric disorders. This review evaluates the most recent available data on cannabinoids utilization in experimental and clinical studies, and highlights their beneficial effects in the prevention of the main neurological diseases and for the clinical treatment of symptoms with them correlated. Full article

(This article belongs to the Section Natural Products Chemistry)

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4460 KiB

Open AccessArticle

Curcumin Protects against CCl₄-Induced Liver Fibrosis in Rats by Inhibiting HIF-1α Through an ERK-Dependent Pathway

by Yanling Zhao, Xiao Ma, Jiabo Wang, Xuan He, Yan Hu, Ping Zhang, Ruilin Wang, Ruisheng Li, Man Gong, Shengqiang Luo and Xiaohe Xiao

Molecules 2014, 19(11), 18767-18780; https://doi.org/10.3390/molecules191118767 - 17 Nov 2014

Cited by 69 | Viewed by 11098

Abstract

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl₄-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of [...] Read more.

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl₄-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1α/ERK pathway in rat liver fibrosis induced by CCl₄. In this study, liver fibrosis was induced by CCl₄ in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and α-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1α and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1α partly through the ERK pathway. Full article

(This article belongs to the Special Issue Curcumin, Inflammation, and Chronic Diseases: How are They Linked?)

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Figure 1

Figure 1
Overview of our study. Full article ">Figure 2
Histological examination of rat livers stained with H&E. (A) Normal group, without any abnormal morphological alternations; (B) Model group, showing marked morphological disruption; (C) CUR-L group, showing moderate regression of morphological changes; (D) CUR-H group, showing marked regression with a large amount of alleviation in the abnormal area. Original magnification 100×. Full article ">Figure 2 Cont.
Histological examination of rat livers stained with H&E. (A) Normal group, without any abnormal morphological alternations; (B) Model group, showing marked morphological disruption; (C) CUR-L group, showing moderate regression of morphological changes; (D) CUR-H group, showing marked regression with a large amount of alleviation in the abnormal area. Original magnification 100×. Full article ">Figure 3
Effects of curcumin on mRNA expression of α-SMA and Col III in liver tissues. The sample tested in this experiment was abstracted from the liver tissues of rats: (A) α-SMA; (B) Col III. Data were expressed as mean ± SD. * p < 0.05, ** p < 0.01 compared with normal group, # p < 0.05, ## p < 0.01 compared with model group. Full article ">Figure 4
Effects of curcumin on the expression of HIF-1α and p-ERK in liver tissues. The protein used in this experiment was extracted from the liver tissues of rats: (A) HIF-1α; (B) p-ERK. Data were expressed as mean ± SD. * p < 0.05, ** p < 0.01 compared with normal group, # p < 0.05, ## p < 0.01 compared with model group. Full article ">Figure 4 Cont.
Effects of curcumin on the expression of HIF-1α and p-ERK in liver tissues. The protein used in this experiment was extracted from the liver tissues of rats: (A) HIF-1α; (B) p-ERK. Data were expressed as mean ± SD. * p < 0.05, ** p < 0.01 compared with normal group, # p < 0.05, ## p < 0.01 compared with model group. Full article ">Figure 5
Cell viability of curcumin on HSC-T6 in vitro. Curcumin marked decreased the viability of HSC-T6 at the concentration of 0.1 μg/mL, and the inhibition increased from 0.05 μg/mL to 1.0 μg/mL. ** p < 0.01 compared with HSC-T6 treated with solvent but no curcumin. Full article ">Figure 6
HIF-1α regulation through the ERK signaling pathway in liver fibrosis. Full article ">

594 KiB

Open AccessReview

The Role of Acyl-Glucose in Anthocyanin Modifications

by Nobuhiro Sasaki, Yuzo Nishizaki, Yoshihiro Ozeki and Taira Miyahara

Molecules 2014, 19(11), 18747-18766; https://doi.org/10.3390/molecules191118747 - 14 Nov 2014

Cited by 79 | Viewed by 11251

Abstract

Higher plants can produce a wide variety of anthocyanin molecules through modification of the six common anthocyanin aglycons that they present. Thus, hydrophilic anthocyanin molecules can be formed and stabilized by glycosylation and acylation. Two types of glycosyltransferase (GT) and acyltransferase (AT) have [...] Read more.

Higher plants can produce a wide variety of anthocyanin molecules through modification of the six common anthocyanin aglycons that they present. Thus, hydrophilic anthocyanin molecules can be formed and stabilized by glycosylation and acylation. Two types of glycosyltransferase (GT) and acyltransferase (AT) have been identified, namely cytoplasmic GT and AT and vacuolar GT and AT. Cytoplasmic GT and AT utilize UDP-sugar and acyl-CoA as donor molecules, respectively, whereas both vacuolar GT and AT use acyl-glucoses as donor molecules. In carnation plants, vacuolar GT uses aromatic acyl-glucoses as the glucose donor in vivo; independently, vacuolar AT uses malylglucose, an aliphatic acyl-glucose, as the acyl-donor. In delphinium and Arabidopsis, p-hydroxybenzoylglucose and sinapoylglucose are used in vivo as bi-functional donor molecules by vacuolar GT and AT, respectively. The evolution of these enzymes has allowed delphinium and Arabidopsis to utilize unique donor molecules for production of highly modified anthocyanins. Full article

(This article belongs to the Special Issue Anthocyanins)

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Figure 1
Representative anthocyanins showing modification by sugar and acyl groups. Full article ">Figure 2
Representative chemical structures of acyl-glucoses. Full article ">Figure 3
Classification of enzymes involved in anthocyanin modification. Full article ">Figure 4
Representative UDP-glucose dependent glucosyltransferase (UGT) reaction for acyl-glucose synthesis. Full article ">Figure 5
Phylogenetic tree analysis of UGTs mediating acyl-glucose production. The tree was constructed from multiple amino acid sequences using the Neighbor-Joining algorithm. The clade of the UGTs involved in acyl-glucose biosynthesis is shown with a gray circle and the others with dark gray circles. UGTs that exhibit acyl-glucose synthesis activity in vitro are marked with asterisks. Full article ">Figure 6
Anthocyanin malylation and glucosylation catalyzed by acyl-glucose dependent transferases in carnation. Full article ">Figure 7
Concatenated units in violdelphin synthesized in a step-by-step reaction utilizing acyl-glucose as both glucosyl and acyl donor in delphinium. Full article ">Figure 8
Sinapoylation and the glucosylation of the p-coumaroyl moiety on the anthocyanin A11 is catalyzed by enzymes using sinapoylglucose as a Zwitter donor in Arabidopsis. Full article ">

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Molecules, Volume 19, Issue 11 (November 2014) – 128 articles , Pages 17066-19252

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