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 mu mol/L. In particular, compound 13f not only has high anti-HIV-1 activity (0.108 mu mol/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. (C) 2014 Yong-Tang Zheng and Xiao-Dong Ma. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved.