Design and Synthesis of Novel N-Arylsulfonyl-3-(2-yl-ethanone)-6-methylindole Derivatives as Inhibitors of HIV-1 Replication

Zhiping Che; Shengming Liu; Yuee Tian; Zhenjie Hu; Yingwu Chen; Genqiang Chen

doi:10.3390/ph8020221

Design and Synthesis of Novel N-Arylsulfonyl-3-(2-yl-ethanone)-6-methylindole Derivatives as Inhibitors of HIV-1 Replication

Pharmaceuticals (Basel). 2015 May 8;8(2):221-9. doi: 10.3390/ph8020221.

Authors

Zhiping Che¹, Shengming Liu¹, Yuee Tian¹, Zhenjie Hu¹, Yingwu Chen¹, Genqiang Chen²

Affiliations

¹ Laboratory of Pharmaceutical Design & Synthesis, Department of Plant Protection, College of Forestry, Henan University of Science and Technology, Luoyang 471003, Henan, China.
² Laboratory of Pharmaceutical Design & Synthesis, Department of Plant Protection, College of Forestry, Henan University of Science and Technology, Luoyang 471003, Henan, China. chgenqiang@sina.com.

Abstract

Seven novel N-arylsulfonyl-3-(2-yl-ethanone)-6-methylindole derivatives 4a-f and 6 were readily synthesized and have been identified as inhibitors of human immunodeficiency virus type-1 (HIV-1) replication. Initial biological studies indicated that among these derivatives, N-(p-ethyl)phenylsulfonyl-3-[2-morpholinoethanone]-6-methylindole (4f) and N-(p-ethyl)phenylsulfonyl-3-[2-(5-phenyl-1,3,4-oxadiazole-2-yl-thio)ethanone]-6-methylindole (6) showed the most promising activity against HIV-1 replication. The effective concentration (EC50) and therapeutic index (TI) values of 4f and 6 were 9.42/4.62 μM, and >49.77/66.95, respectively. The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds.

Keywords: N-arylsulfonyl-3-(2-yl-ethanone)-6-methylindoles; human immunodeficiency virus type-1; inhibitor.