Design, chemical synthesis of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives and biological activity against enoyl-ACP reductase (InhA) and Mycobacterium tuberculosis

摘要

We report here the discovery, synthesis and screening results of a series of 3-(9H-fluoren-9-yl)pyrrolidine-2,5-dione derivatives as a novel class of potent inhibitors of Mycobacterium tuberculosis H37Rv strain as well as the enoyl acyl carrier protein reductase (ENR) InhA. Among them, several compounds displayed good activities against InhA which is one of the key enzymes involved in the type II fatty acid biosynthesis pathway of the mycobacteria cell wall. Furthermore, some exhibited promising activities against M. tuberculosis and multi-drug resistant M. tuberculosis strains.