Computer-assisted design of dual-target anti-HIV-1 compounds

Abstract

Anti-HIV compounds comprise inhibitors of some different biological targets, like HIV protease, integrase and reverse transcriptase enzymes, and entry and fusion proteins. These drugs are usually administered in drug cocktails (AIDS cocktails); the use of a single multi-target anti-HIV-1 compound against AIDS would avoid a more exhaustive therapeutic treatment. The QSAR modeling of reverse transcriptase inhibitors and anti-HIV-1 compounds in general is reported and, given some substructural similarity between the compounds of these two classes, novel compounds with possible double action against HIV-1 were proposed and their bioactivities estimated using the QSAR model. Docking studies were also developed to validate the QSAR predictions, as well as to understand the mode of interaction of the proposed compounds and to compute the docking scores of some derivatives (not predictable using the QSAR model) in the active site of HIV reverse transcriptase.