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Design, synthesis, and antiviral activity of new 1H-1,2,3-triazole nucleoside ribavirin analogs

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Abstract

Ribavirin is a broad antiviral compound with demonstrated activity against herpes simplex virus (HSV), human immunodeficiency virus HIV-1, influenza virus, respiratory syncytial virus, and hepatitis C virus, among other viruses. However, routine clinical use of ribavirin is limited because this compound is considerably cytotoxic. Herein, we describe the design, synthesis, and antiviral activity of new nucleoside ribavirin analogs based on the following: (1) ring bioisosterism of a 1,2,4-triazole for a 1,2,3-triazole; (2) amide group exchange for other substituents, such as c-propyl, methyl carboxylate, or trifluoromethyl groups; and (3) the ribofuranose remained linked to the triazole ring. Compounds 5a–c were obtained with yields of 65–36 % and tested against Influenza A and HSV-1 replication as well as reverse transcriptase (RT) from human immunodeficiency virus type 1 (HIV-1 RT). Compound 5b (R = CO2CH3) was the most effective analog, with IC50 values 14 and 3.8 μM for Influenza A and HIV-1 RT, respectively.

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Acknowledgments

The authors thank the Coordination of Improvement of Higher Education (CAPES), the National Council of R&D of Brazil (CNPq), and Carlos Chagas Filho Foundation for Research of the State of Rio de Janeiro (FAPERJ) for fellowships granted. We also thank the financial support of FAPERJ and Technological Development Program on Products for Health (PDTIS/FIOCRUZ).

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Authors and Affiliations

  1. Departamento de Pesquisa e Desenvolvimento de Fármacos, Fundação Oswaldo Cruz, Instituto de Tecnologia em Fármacos—Farmanguinhos, Manguinhos, Rio de Janeiro, RJ, 21041-250, Brazil

    Maria de Lourdes G. Ferreira, Luiz C. S. Pinheiro, Osvaldo A. Santos-Filho, Marta D. S. Peçanha & Núbia Boechat

  2. Laboratório de Viroses Respiratórias, Fundação Oswaldo Cruz, Instituto Oswaldo Cruz, NIC-WHO, Rio de Janeiro, RJ, Brazil

    Carolina Q. Sacramento, Viviane Machado & Thiago Moreno L. Souza

  3. Departamento de Química Orgânica, Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, CEG, Niterói, RJ, 24210-141, Brazil

    Vitor F. Ferreira

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  1. Maria de Lourdes G. Ferreira
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  2. Luiz C. S. Pinheiro
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  3. Osvaldo A. Santos-Filho
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  6. Viviane Machado
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  7. Vitor F. Ferreira
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  8. Thiago Moreno L. Souza
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  9. Núbia Boechat
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Correspondence to Núbia Boechat.

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de Lourdes G. Ferreira, M., Pinheiro, L.C.S., Santos-Filho, O.A. et al. Design, synthesis, and antiviral activity of new 1H-1,2,3-triazole nucleoside ribavirin analogs. Med Chem Res 23, 1501–1511 (2014). https://doi.org/10.1007/s00044-013-0762-6

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