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.
Interaction of HIV reverse transcriptase with structures mimicking recombination intermediates.
