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Current Topics in Medicinal Chemistry


ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

Research Article

New Efavirenz Derivatives and 1,2,3-Triazolyl-phosphonates as Inhibitors of Reverse Transcriptase of HIV-1

Author(s): Carolina C.P. Costa, Nubia Boechat*, Monica M. Bastos, Fernando de C. da Silva, Andressa Marttorelli, Thiago M.L. Souza, Mayara S. Baptista, Lucas V.B. Hoelz and Ernesto R. Cafffarena

Volume 18, Issue 17, 2018

Page: [1494 - 1505] Pages: 12

DOI: 10.2174/1568026618666181029150118

Price: $65


Background: According to the World Health Organization (WHO), the fight against Acquired Immunodeficiency Syndrome (AIDS) is still one of the most significant challenges facing humanity. Worldwide, it is estimated that 36.7 million people are infected by the Human Immunodeficiency Virus (HIV). Despite the variety of available drugs, the search for new enzymatic inhibitors of HIV is still important due to the presence of adverse effects and the development of resistant strains. Therefore, the present study aimed to design, synthesize, and biologically evaluate novel inhibitors of HIV Reverse Transcriptase (RT).

Materials and Methods: These compounds were obtained in two series, and compounds in both series contain a 1,2,3-triazole ring in their structures. The compounds in the first series are Efavirenz (EFV) analogues with the N-1 position substituted by another important fragment as described in the medicinal chemistry literature on anti-HIV drugs. The second series has a phosphonate chain similar to that in the structure of Tenofovir Disoproxil Fumarate (TDF).

Results and Conclusion: The results of the biological evaluation showed that all compounds presented high RT inhibition values and lower or comparable inhibitory concentrations (the concentration needed to reduce the enzymatic activity by 50%, IC50 values, 0.8-1.9 µM). Among the compounds in the first series, the three with the lowest IC50 values had values between 0.8-0.9 µM, and of those in the second series, the most potent had an IC50 value of 1.1 µM; compounds in both series were equipotent to TDF (1.2 µM). Thus, the new compounds could be considered lead compounds for the development of new antiretroviral compounds.

Keywords: HIV-1, Reverse transcriptase, Efavirenz, Tenofovir disoproxil fumarate, 1, 2, 3-triazoles, Click chemistry.

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