Development of acridine derivatives as selective Mycobacterium tuberculosis DNA gyrase inhibitors

Bioorganic & Medicinal Chemistry
Brahmam MedapiDharmarajan Sriram

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.

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Nov 1, 2007·Infectious Disorders Drug Targets·Khisimuzi Mdluli, Zhenkun Ma
Feb 7, 2012·Biochemistry·Adam C KetronNeil Osheroff
Jul 3, 2015·Therapeutic Advances in Chronic Disease·Stephen K Field

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Citations

Dec 1, 2017·Frontiers in Molecular Biosciences·Michael A ReicheValerie Mizrahi
Jun 21, 2019·Nature·Eachan O JohnsonDeborah T Hung
May 26, 2020·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Andrés-Felipe Villamizar-MogotocoroVladimir V Kouznetsov
Nov 5, 2020·Bioorganic Chemistry·Shalini JaswalVikramdeep Monga

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