Synthesis of 3-heteroarylthioquinoline derivatives and their in vitro antituberculosis and cytotoxicity studies.

摘要

A series of 3-heteroarylthioquinoline derivatives has been synthesized by the Friedlander annulation of 2-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]-1-aryl-1-ethanone/2-(1,3-benzothiazo l-2-ylsulfanyl)-1-aryl-1-ethanone/1-aryl-2-[(2-phenyl-2H-1,2,3,4-tetraazol-5-yl)s ulfanyl]-1-ethanone with 2-aminobenzophenone in good yields using YbCl(3) as the catalyst. These compounds have been screened for their in vitro activity against Mycobacterium tuberculosis H37Rv (MTB) and among the 21 compounds screened, 2-[2-(4-bromophenyl)-4-phenyl-3-quinolyl]sulfanyl-5-methyl-1,3,4-thiadiazole (5d) and 2-[2-(4-chlorophenyl)-4-phenyl-3-quinolyl]sulfanyl-5-methyl-1,3,4-thiadiazole (5c) were found to be the most active compounds with MIC of 3.2 and 3.5 muM respectively against MTB. The cytotoxic effects against mouse fibroblasts (NIH 3T3) in vitro were evaluated for 5c and 5d, which displayed no toxic effects (IC(50) > 1000 muM) against the mouse fibroblast cell line NIH 3T3.