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ID: ALA3751721

Journal: Bioorg Med Chem

Title: Development of acridine derivatives as selective Mycobacterium tuberculosis DNA gyrase inhibitors.

Authors: Medapi B, Meda N, Kulkarni P, Yogeeswari P, Sriram D.

Abstract: 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.

CiteXplore: 26787274

DOI: 10.1016/j.bmc.2016.01.011