[go: up one dir, main page]
More Web Proxy on the site http://driver.im/ Skip to main content
Springer Nature Link
Log in

Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

New amide linked bis-indoles 10a, b, and 12 have been synthesized by treatment of tryptamine (9) or 5-aminoindole (11) with oxalyl chloride or adipoyl chloride. In addition, a newly indole derivatives 14–16 incorporated or fused with coumarin moieties have been prepared through the reaction of 9 or 11 with 4-chloro-3-formylcoumarin (13a) or 4-chloro-3-nitrocoumarin (13b). Further, 13-(3-nitrophenyl)-6,13-dihydrochromeno[4,3-b]pyrrolo[3,2-f]quinolin-12(3H)-one (20) has been produced via one-pot Mannish reaction of 11, 4-hydroxycoumarin (17), and 3-nitrobenzaldehyde (18) in the presence of N-chlorosuccinimide (NCS) as a catalyst. A mixture of 3-[(3H-indol-3-ylidene)methyl]-4-hydroxy-2H-chromen-2-one (24A), and 3-[(1H-indol-3-yl)methylene]chroman-2,4-dione (24B) has been obtained with ratio 1:1 through Knoevenagel condensation reaction of indole-3-carboxaldehyde (21) and 17. Structures of the obtained compounds have been assigned by sophisticated spectroscopic techniques (1H-NMR, 13C-NMR, and 2D NMR) and mass spectrometry. All the synthesized compounds have been screened for their cytotoxic activity against the human cervix carcinoma cell line (KB-3-1), where compounds 14a, 16, and 20 exhibit the highest potent activity (IC50 = 1.8, 2.2, and 7.9 µM, respectively) in comparison with the positive control (+)-Griseofulvin (IC50 = 19.2 µM), whereas the tautomeric mixture 24A, B show moderate activity (IC50 = 71.3 µM). Moreover, molecular docking study of the synthesized compounds toward the matrix metalloproteinase-8 (MMP-8) (PDB ID: 1MNC) has also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Scheme 1
Scheme 2
Scheme 3
Scheme 4
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Abdolmohammadi S (2014) Silica supported Zr(HSO4)4 catalyzed solvent-free synthesis of [1]benzopyrano[4,3-b][1]benzopyran-6-ones and xanthenones. J Org Chem 11:350–355

    CAS  Google Scholar 

  • Abdou MM, El-Saeed RA, Bondock S (2015) Recent advances in 4-hydroxycoumarin chemistry. Part 2: scaffolds for heterocycle molecular diversity. Arab J Chem. https://doi.org/10.1016/j.arabjc.2015.06.029

  • Abdou MM, Bondock S, El-Desouky SI, Metwally MA (2013) Synthesis, spectroscopic studies and technical evaluation of novel disazo disperse dyes derived from 3-(2-hydroxyphenyl)-2-pyrazolin-5-ones for dyeing polyester fabrics. Am J Chem 3:59–67

    CAS  Google Scholar 

  • Arya AK, Rana K, Kumar M (2014) A facile synthesis and anticancer activity evaluation of spiro analogs of benzothiazolylchromeno/pyrano derivatives. Lett Drug Des Discov 11:594–600

    Article  CAS  Google Scholar 

  • Awantu AF, Lenta BN, Bogner T, Fongang YF, Ngouela S, Wansi JD, Tsamo E, Sewald N et al. (2011) Dialiumoside, an olean-18-ene triterpenoid from dialiumexcelsum. Z Naturforsch 66b:624–628

    Article  Google Scholar 

  • Bell R, Carmeli S, Sar N (1994) Vibrindole A, a metabolite of the marine bacterium, vibrio parahaemolyticus, isolated from the toxic mucus of the Boxfish ostracioncubicus. J Nat Prod 57:1587–1590

    Article  CAS  PubMed  Google Scholar 

  • Blunt JW, Copp BR, Munro MH, Northcote PT, Prinsep MR (2011) Marine natural products. Nat Prod Rep 28:196–268

    Article  CAS  PubMed  Google Scholar 

  • Bredt AB, Girey GJ (1982) Antipyretic effects of indomethacin in liver metastases of solid tumors. Cancer 50:1430–1433

    Article  CAS  PubMed  Google Scholar 

  • Caron S, Vazquez E, Stevens RW, Nakao K, Koike H, Murata Y (2003) Efficient synthesis of [6-Chloro-2-(4-chlorobenzoyl)-1H-indol-3-yl]-acetic acid, a novel COX-2 inhibitor. J Org Chem 68:4104–4107

    Article  CAS  PubMed  Google Scholar 

  • Dawara L, Singh RV (2011) Synthesis, spectroscopic characterization, antimicrobial, pesticidal and nematicidal activity of some nitrogen-oxygen and nitrogen-sulfur donor coumarins based ligands and their organotin (IV) complexes. App Organomet Chem 25:643–652

    CAS  Google Scholar 

  • Decock J, Hendrickx W, Thirkettle S, Gutiérrez-Fernández A, Robinson SD, Edwards DR et al. (2015) Pleiotropic functions of the tumor- and metastasis-suppressing matrix metalloproteinase-8 in mammary cancer in MMTV-PyMT transgenic mice. Breast Cancer Res 17:1–13

    Article  CAS  Google Scholar 

  • Dekic B, Dekic V, Radulovic N, Vukic evic R, Palic R (2010) Synthesis of new antimicrobial 4-aminosubstituted 3-nitrocoumarins. Chem Pap 64:354–359

    Article  CAS  Google Scholar 

  • Diana D, Carbone A, Barraja P, Kelter G, Fiebig HH, CirrincioneG (2010) Synthesis and antitumor activity of 2,5-bis(3′-indolyl)-furans and 3,5-bis(3′-indolyl)-isoxazoles, nortopsentin analogs. Bioorg Med Chem 18:4524–4529

    Article  CAS  PubMed  Google Scholar 

  • Endo T, Tsuda M, Fromont J, Kobayashi J (2007) Hyrtinadine A, a bis-indole alkaloid from a marine sponge. J Nat Prod 70:423–424

    Article  CAS  PubMed  Google Scholar 

  • Ghanei-Nasab S, Khoobi M, Hadizadeh F, Marjani A, Moradi A, Nadri H, Emami S, Foroumadi A, Shafiee A (2016) Synthesis and anticholinesterase activity of coumarin-3-carboxamides bearing tryptamine moiety. Eur J Med Chem 121:40–46

    Article  CAS  PubMed  Google Scholar 

  • Gul W, Hamann MT (2005) Indole alkaloid marine natural products: an established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases. Life Sci 78:442–453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guo WHZ, Yi X, Guo C, Chu F, Cheng G (2003) Discovery of 2-phenyl-3-sulfonylphenyl-indole derivatives as a new class of selective COX-2 inhibitors. Bioorg Med Chem 11:5539–5544

    Article  PubMed  Google Scholar 

  • Hatti I, Sreenivasulu R, Jadav SS, Ahsan MJ, Raju RR (2015) Synthesis and biological evaluation of 1,3,4-oxadiazole-linked bisindole derivatives as anticancer agents. Monatsh Chem 146:1699–1705

    Article  CAS  Google Scholar 

  • Kandemir H, Sengul IF, Kumar N, Black DS (2016) Synthesis of a 7-(aminomethyl)indole and related bis-indole derivatives. ARKIVOC iv:288–295

    Google Scholar 

  • Khurana JM, Kumar S (2009) Tetrabutylammonium bromide (TBAB): a neutral and efficient catalyst for the synthesis of biscoumarin and 3,4-dihydropyrano[c]chromene derivatives in water and solvent-free conditions. Tetrahedron Lett 50:4125–4127

    Article  CAS  Google Scholar 

  • Kidwai M, Jain A, Singh S, Nemaysh V, Luthra PM (2014) An investigatory study of antibacterial activity of functionalized spirooxindoles. Indian J Chem Sect B 53:399–411

    Google Scholar 

  • Kumar S, Mehndiratta S, Nepali K, Gupta MK, Koul S, Sharma PR, Saxena AK, Dhar KD (2013) Novel indole-bearing combretastatin analogs as tubulin polymerization inhibitors. Org Med Chem Lett 3:3–16

    Article  PubMed  PubMed Central  Google Scholar 

  • Lebedev VS, Milevskii BG, Soloveva NP, Chibisova TA, Kazheva ON, Dyachenko OA, Alexandrov GG, Traven VF (2014) Tautomeric forms of 3-formyl-4-hydroxycoumarin arylhydrazones. Chem Heterocycl Compd 50:1081–1089

    Article  CAS  Google Scholar 

  • Mansoor SS, Logaiya K, Sudhan SPN, Aswin K (2015) Succinimide-N-sulfonic acid as an efficient recyclable catalyst for the synthesis of some fused indole pyranopyrimidinone derivatives. Bull Chem Soc Ethiop 29:457–471

    Article  CAS  Google Scholar 

  • McDougal A, Gupta MS, Morrow DK, Ramamoorthy K, Lee JE, Safe SH (2001) Methyl‐substituted diindolyl-methanes as inhibitors of estrogen‐induced growth of T47D cells and mammary tumors in rats. Breast Cancer Res Treat 66:147–157

    Article  CAS  PubMed  Google Scholar 

  • Plamisano G, Tibiletti F, Penoni A, Colombo F, Tollari S, Garella D, Tagliapietra S, Cravotto G (2010) Ultrasound-enhanced one-pot synthesis of 3-(Het)arylmethyl-4-hydroxycoumarins in water. Ultrason Sonochem 18:652–660

    Article  Google Scholar 

  • Safe S, Papineni S, Chintharlapalli S (2008) Cancer chemotherapy with indole-3-carbinol, bis(3’-indolyl)methane and synthetic analogs. Cancer Lett 269:326–338

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Salman AS, Mahmoud NA, Abdel-Aziem A, Mohamed MA, Elsisi DM (2015) Synthesis, reactions and antimicrobial activity of some new 3-substituted indole derivatives. Int J Org Chem 5:81–99

    Article  CAS  Google Scholar 

  • Sammet B, Bogner T, Nahrwold M, Weiss C, Sewald N (2010) Approaches for the synthesis of functionalized cryptophycins. J Org Chem 75:6953–6960

    Article  CAS  PubMed  Google Scholar 

  • Senol FS, Yilmaz G, Sener B, Koyuncu M, Orhan I (2010) Preliminary screening of acetylcholinesterase inhibitory and antioxidant activities of Anatolian Heptaptera species. Pharm Biol 48:337–341

    Article  CAS  PubMed  Google Scholar 

  • Shin J, Seo Y, Cho KW, Rho JR, Sim CJ (1996) New bis(indole) alkaloids of the topsentin class from the sponge spongosorites genitrix. J Nat Prod 62:647–649

    Article  Google Scholar 

  • Sugiyama Y, Ito Y, Suzuki M, Hirota A (2009) Indole derivatives from a marine sponge-derived yeast as DPPH radical scavengers. J Nat Prod 72:2069–2071

    Article  CAS  PubMed  Google Scholar 

  • Sujatha K, Perumal PT, Muralidharan D, Rajendra M (2009) Synthesis, analgesic and antiinflamatory activities of bis (indolyl) methanes. Indian J Chem 48B:267–272

    CAS  Google Scholar 

  • Sundberg RJ (1996) The Chemistry of indoles. Academic Press, New York, NY

    Google Scholar 

  • Vilar S, Cozza G, Moro S (2008) Medicinal chemistry and the molecular operating environment (MOE): application of QSAR and molecular docking to drug discovery. Curr Top Med Chem 8:1555–1572

    Article  CAS  PubMed  Google Scholar 

  • Wang XS, Zhang MM, Zeng ZS, Shi DQ, Tu SJ, Wei XJ, Zong ZM (2005) A clean procedure for the synthesis of chromeno[4,3-b]benzo[f]quinolone and quinolino[4,3-b]benzo[f]quinoline derivatives in aqueous media. Chem Lett 34:1316–1317

    Article  CAS  Google Scholar 

  • Zhou S, Klaunig JE (2016) Interplay between MMP-8 and TGF-β1 and its role in regulation of epithelial to mesenchymal transition in hepatocellular carcinoma. Transl Cancer Res 5:S1135–S1138

    Article  CAS  Google Scholar 

  • Zhuang Q, Zhou D, Tu S, Li C, Cao L, Shao Q (2008) A highly efficient microwave-assisted synthesis of chromeno[3,4-b][4,7]phenanthroline derivatives through multicomponent reactions in water. J Heterocycl Chem 45:831–835

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors are grateful to the NMR and MS Departments at Bielefeld University for spectral measurements. We would like to thank Carmela Michalek for biological activity testing and Marco Wißbrock with Anke Nieß for technical assistance. This research work has been financed by the German Academic Exchange Service (DAAD) with funds from the German Federal Foreign Office in the frame of the Research Training Network “Novel Cytotoxic Drugs from Extremophilic Actinomycetes” (Project ID57166072).

Author information

Authors and Affiliations

  1. Chemistry Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11884, Egypt

    Ahmed H. Halawa, Ahmed H. Bedair, Essam M. Eliwa & Ahmed M. El-Agrody

  2. Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy (Girls), Al-Azhar University, Nasr City, Cairo, 11754, Egypt

    Shimaa M. Abd El-Gilil

  3. Organic and Bioorganic Chemistry, Faculty of Chemistry, Bielefeld University, Bielefeld, 33501, Germany

    Essam M. Eliwa, Marcel Frese, Norbert Sewald & Mohamed Shaaban

  4. Chemistry of Natural Compounds Department, Division of Pharmaceutical Industries, National Research Centre, El-Behoos St. 33, Dokki, Cairo, 12622, Egypt

    Mohamed Shaaban

Authors
  1. Ahmed H. Halawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shimaa M. Abd El-Gilil
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ahmed H. Bedair
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Essam M. Eliwa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marcel Frese
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Norbert Sewald
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mohamed Shaaban
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Ahmed M. El-Agrody
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ahmed M. El-Agrody.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Halawa, A.H., Abd El-Gilil, S.M., Bedair, A.H. et al. Synthesis of diverse amide linked bis-indoles and indole derivatives bearing coumarin-based moiety: cytotoxicity and molecular docking investigations. Med Chem Res 27, 796–806 (2018). https://doi.org/10.1007/s00044-017-2103-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-017-2103-7

Keywords

Search

Navigation