Synthesis and anti-HIV Evaluation of substituted indole-3-carbaldehyde derivatives

In the present study, a series of indole-3-carbaldehydes having substituted N-sulfonyl phenyl or Nphenacyl group was synthesized and evaluated for anti-HIV activity, in particular, in vitro and in silico HIV-1 integrase inhibition. Three compounds (8b, 8c and 8g) exhibited significant inhibition of HIV-1 IN (IC50 ≤5.32 μM). Molecular docking studies were also performed to justify the IN inhibition and in vitro in silico correlation was drawn. Compound 8b exhibited significant anti-HIV activity against HIV-1 strain IIIB (IC50 3.16 μM). HIV integrase inhibitors are also reported to inhibit reverse transcriptase. When 8b was further examined against various single and double mutant reverse transcriptase (RT) strains, it showed promising activity against E138K with IC50 value of 2.43 μM with safety index of 3. Therefore, compound 8b can be a starting point for the development of dual inhibitors of HIV integrase as well as reverse transcriptase.