Synthesis of some benzimidazole derivatives endowed with 1,2,3-triazole as potential inhibitors of hepatitis C virus

Youssif, Bahaa G. M.; Mohamed, Yaseen A. M.; Salim, Mohammed T. A.; Inagaki, Fuyuhiko; Mukai, Chisato; Abdu-Allah, Hajjaj H. M.

doi:10.1515/acph-2016-0014

Abstract

New derivatives of 2-thiobenzimidazole incorporating triazole moiety were synthesized, characterized and tested in vitro for antiviral activity against hepatitis C virus (HCV) and hepatitis B virus (HBV). Their cytotoxicity was determined by the reduction in the number of viable cell. All of the synthesized compounds are inactive against HBV and some showed activity against HCV. In particular, two compounds showed significant activity, 2-{4-[(1-benzoylbenzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitro-phenyl)-acetamide (13) and 2-(4-{[1-(p-chlorobenzoyl)-benzimidazol-2-ylthio)methyl]-1H-1,2,3-triazol-1-yl}-N-(p-nitrophenyl)-acetamide (17). The results give an insight into the importance of the substituent at position 2 of benzimidazole for the inhibition of HCV.

References

1. J. S. Au and P. J. Pockros, Novel therapeutic approaches for hepatitis C, Clin. Pharmacol. Ther. 95 (2014) 78–88; DOI: 10.1038/clpt.2013.206.10.1038/clpt.2013.206
Search in Google Scholar
2. M. P. Manns, J. G. McHutchison, S. C. Gordon, V. K. Rustgi, M. Shiffman, R. Reindollar, Z. D. Goodman, K. Koury, M. Ling and J. K. Albrecht, Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial, Lancet358 (2001) 958–965.10.1016/S0140-6736(01)06102-5
Search in Google Scholar
3. M. W. Fried, M. L. Shiffman, K. R. Reddy, C. Smith, G. Marinos, F. L. Gonçales Jr., D. Häussinger, M. Diago, G. Carosi, D. Dhumeaux, A. Craxi, A. Lin, J. Hoffman and J. Yu, Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection, N. Engl. J. Med.347 (2002) 975–982; DOI: 10.1056/NEJMoa020047.10.1056/NEJMoa020047
Search in Google Scholar
4. Y. Bansal and O. Silakari, The therapeutic journey of benzimidazoles: A review, Bioorg. Med. Chem.20 (2012) 6208–6236; DOI: 10.1016/j.bmc.2012.09.013.10.1016/j.bmc.2012.09.013
Search in Google Scholar
5. V. Boido, G. Paglietti, M. Tonelli and G. Vitale, Non-nucleoside Benzimidazoles as Antiviral Drugs Against HCV and RSV Infections, in RNA-Viruses. Enzymatic and Receptoral Inhibitors (Ed. A. Carta), Research Signpost, Kerala 2009, pp. 41–93.
Search in Google Scholar
6. B. A. Katz, J. Clark, J. Finer-Moore, T. Jenkins, C. Johnson, M. Ross, C. Luong, W. Moore and R. Stroud, Design of potent selective zinc-mediated serine protease inhibitors, Nature391 (1998) 608–612; DOI: 10.1038/35422.10.1038/35422
Search in Google Scholar
7. D. Sperandio, A. R. Gangloff, J. Litvak, R. Goldsmith, J. M. Hataye, V. R. Wang, E. J. Shelton, K. Elrod, J. W. Janc, J. M. Clark, K. Rice, S. Weinheimer, K. Yeung, N. A. Meanwell, D. Hernandez, A. J. Staab, B. L. Venables and J. R. Spencer, Highly potent non-peptidic inhibitors of the HCV NS3/NS4A serine protease, Bioorg. Med. Chem. Lett.12 (2002) 3129–3133; DOI: 10.1016/S0960-894X(02)00680-7.10.1016/S0960-894X(02)00680-7
Search in Google Scholar
8. H. I. El Diwani, H. T. Abdel-Mohsen, I. Salama, F. A.-F. Ragab, M. M. Ramla, S. A. Galal, M. M. Abdalla, A. Abdel-Wahab and M. A. El Demellawy, Synthesis, molecular modeling, and biological evaluation of novel benzimidazole derivatives as inhibitors of hepatitis C virus RNA replication, Chem. Pharm. Bull.62 (2014) 856–866; DOI: 10.1248/cpb.c13-01009.10.1248/cpb.c13-01009
Search in Google Scholar
9. L. Garuti, M. Roberti and G. Gentilomi, Synthesis and antiviral assays of some 2-substituted benzimidazole-N-carbamates, Farmaco55 (2000) 35–39; DOI: 10.1016/S0014-827X(99)00117-2.10.1016/S0014-827X(99)00117-2
Search in Google Scholar
10. S. Budow, M. Kozlowska, A. Gorska, Z. Kazimierczuk, H. Eickmeier, P. La Colla, G. Gosselin and F. Seela, Substituted benzimidazole: antivral activity and synthesis of nucleosides, ARKIVOC iii (2009) 225–250; DOI: 10.3998/ark.5550190.0010.319.10.3998/ark.5550190.0010.319
Search in Google Scholar
11. M. F. Tonelli, F. Novelli, B. Tasso, I. Vazzana, A. Sparatore, V. Boido, F. Sparatore, P. La Colla, G. Sanna, G. Giliberti, B. Busonera, P. Farci, C. Ibba and R. Loddo, Antiviral activity of benzimidazole derivatives. III. Novel anti-CVB-5, anti-RSV and anti-Sb-1 agents, Bioorg. Med. Chem.22 (2014) 4893–4909; DOI: 10.1016/j.bmc.2014.06.043.10.1016/j.bmc.2014.06.04325082514
Search in Google Scholar
12. Y. Saito, V. Escuret, D. Durantel, F. Zoulim, R. F. Schinazic and L. A. Agrofoglio, Synthesis of 1,2,3-triazolo-carbanucleoside analogues of ribavirin targeting an HCV in replicon, Bioorg. Med. Chem.11 (2003) 3633–3639; DOI: 10.1016/S0968-0896(03)00349-3.10.1016/S0968-0896(03)00349-3
Search in Google Scholar
13. F. D. Da Silva, M. C. B. V. de Souza, I. I. P. Frugulhetti, H. C. Castro, S. L. D Souza, T. M. L. de Souza, D. Q. Rodrigues, A. M. T. Souza, P. A. Abreu, F. Passamani, C. R. Rodrigues and V. F. Ferreira, Synthesis, HIV-RT inhibitory activity and SAR of 1-benzyl-1H-1,2,3-triazole derivatives of carbohydrates, Eur. J. Med. Chem.44 (2009) 373–383; DOI: 10.1016/j.ejmech.2008.02.047.10.1016/j.ejmech.2008.02.047
Search in Google Scholar
14. D. K. Mohapatra, P. K. Maity, M. Shabab and M. I. Khan, Click chemistry based rapid one-pot synthesis and evaluation for protease inhibition of new tetracyclic triazole fused benzodiazepine derivatives, Bioorg. Med. Chem.19 (2009) 5241–5245; DOI: 10.1016/j.bmcl.2009.06.107.10.1016/j.bmcl.2009.06.107
Search in Google Scholar
15. T. O. Olomola, R. Klein, K. A. Lobb, Y. Sayed and P. T. Kaye, Synthesis and evaluation of coumarin derivatives as potential dual-action HIV-1 protease and reverse transcriptase inhibitors, Bioorg. Med. Chem.21 (2013) 1964–1971; DOI: 10.1016/j.bmc.2013.01.025.10.1016/j.bmc.2013.01.025
Search in Google Scholar
16. M. M. Heravi, A. Keivanloo, M. Rahimizadeh, M. Bakavoli and M. Ghassemzadeh, Pd–Cu catalyzed heterocyclization during Sonogashira coupling: synthesis of 3-benzylthiazolo[3,2-a]benzimidazole, Tetrahedron Lett.45 (2004) 5747–5749; DOI: 10.1016/j.tetlet.2004.05.094.10.1016/j.tetlet.2004.05.094
Search in Google Scholar
17. K.-C. Tiew, D. Dou, T. Teramoto, H. Lai, K. R. Alliston, G. H. Lushington, R. Padmanabhan and W. C. Groutas, Inhibition of Dengue virus and West Nile virus proteases by click chemistry-derived benz[d] isothiazol-3(2H)-one derivatives, Bioorg. Med. Chem.20 (2012) 1213–1221; DOI: 10.1016/j.bmc.2011.12.047.10.1016/j.bmc.2011.12.047
Search in Google Scholar
18. C. Baba, K. Yanagida, T. Kanzaki and M. Baba, Colorimetric lactate dehydrogenase (LDH) assay for evaluation of antiviral activity against bovine viral diarrhoea virus (BVDV) in vitro, Antivir. Chem. Chemother.16 (2005) 33–39; DOI: 10.1016/j.biomaterials.2014.01.054.10.1016/j.biomaterials.2014.01.054
Search in Google Scholar
19. K. Sako, H. Aoyama, S. Sato, Y. Hashimoto and M. Baba, γ-carboline derivatives with anti-bovine viral diarrhea virus (BVDV) activity, Bioorg. Med. Chem.16 (2008) 3780–3790; DOI: 10.1016/j.bmc.2008.01.052.10.1016/j.bmc.2008.01.052
Search in Google Scholar
20. H. C. Kolb, M. G. Finn and K. B. Sharpless, Click chemistry: Diverse chemical function from a few good reactions, Angew. Chem. Int. Ed.40 (2001) 2004–2021; DOI: 10.1002/1521-3773(20010601)40:11<;2004::AID-ANIE2004>3.0.CO;2-5.10.1002/1521-3773(20010601)40:11<;2004::AID-ANIE2004>3.0.CO;2-5
Search in Google Scholar
21. J. E. Moses and A. D. Moorhouse, The growing applications of click chemistry, Chem. Soc. Rev.36 (2007) 1249–1262; DOI: 10.1039/b613014n.10.1039/B613014N
Search in Google Scholar
22. S. G. Agalave, S. R. Maujan and V. S. Pore, Click chemistry: 1,2,3-Triazoles as pharmacophores, Chem. Asian J.6 (2011) 2696–2718; DOI: 10.1002/asia.201100432.10.1002/asia.20110043221954075
Search in Google Scholar
23. J.-F. Lutz and Z. Zarafshani, Efficient construction of therapeutics, bioconjugates, biomaterials and bioactive surfaces using azide-alkyne “click” chemistry, Adv. Drug Deliv. Rev.60 (2008) 958–970; DOI: 10.1016/j.addr.2008.02.004.10.1016/j.addr.2008.02.00418406491
Search in Google Scholar
24. K. Lin, R. B. Perni, A. D. Kwong and c. Lin, VX-950, a novel hepatitis C virus (HCV) NS3-4A protease inhibitor, exhibits potent antiviral activities in HCV replicon cells, Antimicrob. Agents. Cli.50 (2006) 1813–1822; DOI: 10.1128/AAC.50.5.1813-1822.2006.10.1128/AAC.50.5.1813-1822.2006147222716641454
Search in Google Scholar
25. J. G. Topliss, Utilization of operational schemes for analog synthesis in drug design, J. Med. Chem.15 (1972) 1006–1011; DOI: 10.1021/jm00280a002.10.1021/jm00280a0025069767
Search in Google Scholar
26. J. G. Topliss, A manual method for applying the Hansch approach to drug design, J. Med. Chem.20 (1977) 463–469; DOI: 10.1021/jm00214a001.10.1021/jm00214a001321782
Search in Google Scholar

Synthesis of some benzimidazole derivatives endowed with 1,2,3-triazole as potential inhibitors of hepatitis C virus

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