Identification of the novel N-phenylbenzenesulfonamide derivatives as potent HIV inhibitors

Searching for more safe and effective agents for HIV treatments is still an urgent topic worldwide. Based on our continuous modifications on the benzophenone derivatives as HIV-1 reverse transcriptase (RT) inhibitors, a new template bearing N-phenylbenzenesulfonamide (PBSA) structure was designed to enhance the interactions with HIV-1 RT. In this manuscript, a series of PBSA derivatives were synthesized and evaluated for their anti-HIV-1 activity. The preliminary test showed that these compounds were potent to inhibit wild-type HIV-1 with EC50 values ranging of 0.105–14.531 μmol/L. In particular, compound 13f not only has high anti-HIV-1 activity (0.108 μmol/L), but also possesses low toxicity with a TI value of 1816.6. Furthermore, the major interactions of the inhibitor 13f with HIV-1 RT were also investigated using the molecular modelling. Our discovered structure-activity relationships (SARs) of these analogues may serve as an important clue for further optimizations.

Graphical abstractA new template bearing N-phenylbenzenesulfonamide (PBSA) structure was designed to enhance the interactions with HIV-1 RT. Anti-HIV evaluation indicated that these compounds were potent to inhibit wild-type HIV-1 with EC50 values ranging from 0.105 μmol/L to 14.531 μmol/L.Figure optionsDownload full-size imageDownload as PowerPoint slide