Discovery of N-arylsulfonyl-3-acylindole benzoyl hydrazone derivatives as anti-HIV-1 agents

The discovery and development of novel inhibitors with activity against variants of human immunodeficiency virus type 1 (HIV-1) is pivotal for overcoming treatment failure. As our ongoing work on research of anti-HIV-1 inhibitors, 32 N-arylsulfonyl-3-acylindole benzoyl hydrazone derivatives were prepared by introduction of the hydrazone fragments on the N-arylsulfonyl-3-acylindolyl skeleton and preliminarily screened in vitro as HIV-1 inhibitors for the first time. Among of all the reported analogues, eight compounds exhibited significant anti-HIV-1 activity, especially N-(3-nitro) phenylsulfonyl-3-acetylindole benzoyl hydrazone (18) and N-(3-nitro) phenylsulfonyl-3-acetyl-6-methylindole benzoyl hydrazone (23) displayed the most potent anti-HIV-1 activity with EC50 values of 0.26 and 0.31 mu g/mL, and TI values of > 769.23 and > 645.16, respectively. It is noteworthy that introduction of R-3 as the methyl group and R-2 as the hydrogen group could result in more potent compounds. This suggested that introduction of R-3 as the methyl group could be taken into account for further preparation of these kinds of compounds as anti-HIV-1 agents.