piperidines and 2-chlorobenzoic-acid

In this study we have designed p-phenylene diamine linked acridine derivative from our earlier reported quinoline-aminopiperidine hybrid MTB DNA gyrase inhibitors with aiming more potency and less cardiotoxicity. We synthesized thirty six compounds using four step synthesis from 2-chloro benzoic acid. Among them compound 4-chloro-N-(4-((2-methylacridin-9-yl)amino)phenyl)benzenesulphonamide (6) was found to be more potent with MTB DNA gyrase super coiling IC50 of 5.21±0.51μM; MTB MIC of 6.59μM and no zHERG cardiotoxicity at 30μM and 11.78% inhibition at 50μM against mouse macrophage cell line RAW 264.7.

Topics: Acridines; Animals; Antitubercular Agents; Bacterial Proteins; Cell Line; Cell Survival; Chlorobenzoates; DNA Gyrase; Dose-Response Relationship, Drug; Embryo, Nonmammalian; Ether-A-Go-Go Potassium Channels; Gene Expression; Heart Rate; Macrophages; Mice; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Piperidines; Quinolines; Structure-Activity Relationship; Topoisomerase II Inhibitors; Zebrafish; Zebrafish Proteins