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Identification of 1-Aryl-1H-1,2,3-triazoles as Potential New Antiretroviral Agents

[ Vol. 14 , Issue. 3 ]

Author(s):

Daniel T.G. Gonzaga, Thiago M.L. Souza, Viviane M.M. Andrade, Vitor F. Ferreira and Fernando de C. da Silva*   Pages 242 - 248 ( 7 )

Abstract:


Background: Low molecular weight 1-Aryl-1H-1,2,3-triazoles are endowed with various types of biological activities, such as against cancer, HIV and bacteria. Despite the existence of six different classes of antiretroviral drugs in clinical use, HIV/AIDS continue to be an on growing public health problem.

Objective: In the present study, we synthesized and evaluated thirty 1-Aryl-1H-1,2,3-triazoles against HIV replication.

Method: The compounds were prepared by Huisgen 1,3-dipolar cycloaddition protocol catalyzed by Cu(I) between aryl azides and propargylic alcohol followed by further esterification and etherification from a nucleophilic substitution with acid chlorides or alkyl bromides in good yields. The compounds were submitted to the inhibition of HIV replication and evaluation of their cytotoxicity. Initially, the compounds were screened at 10 µM and the most active were further evaluated in order to obtain some pharmacological parameters.

Results: Thirty molecules were evaluated, six were selected – because they inhibited more than 80% HIV replication. We further showed that two of these compounds are 8-times more potent, and less cytotoxic, than nevirapine, an antiretroviral drug in clinical use.

Conclusion: We identified very simple triazoles with promissing antiretroviral activities that led to the development of new drugs against AIDS.

Keywords:

AIDS, antiretroviral agents, antiretroviral drug, Copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), Huisgen cycloaddition, inhibition of HIV.

Affiliation:

Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, 24020-150, Niteroi-RJ, Fundacao Oswaldo Cruz, Presidencia da Fiocruz, Centro de Desenvolvimento Tecnologico em Saude, Instituto Oswaldo Cruz, Laboratorio de Imunofarmacologia, 21040-360 - Rio de Janeiro-RJ, Fundacao Oswaldo Cruz, Presidencia da Fiocruz, Centro de Desenvolvimento Tecnologico em Saude, Instituto Oswaldo Cruz, Laboratorio de Imunofarmacologia, 21040-360 - Rio de Janeiro-RJ, Universidade Federal Fluminense, Departamento de Tecnologia Farmaceutica, Faculdade de Farmacia, 24241-002, Niteroi-RJ, Universidade Federal Fluminense, Departamento de Quimica Organica, Instituto de Quimica, Campus do Valonguinho, 24020-150, Niteroi-RJ

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