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The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis.

ABSTRACT: We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90) as low as 5.1 ?M and no cytotoxicity against eukaryotic cells (IC50 > 50 ?M). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. Mutations suggest that Ndh may be the target of this series.

SUBMITTER: Korkegian A

PROVIDER: S-EPMC5854369 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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The 7-phenyl benzoxaborole series is active against Mycobacterium tuberculosis.

Korkegian Aaron A O'Malley Theresa T Xia Yi Y Zhou Yasheen Y Carter David S DS Sunde Bjorn B Flint Lindsay L Thompson Dean D Ioerger Thomas R TR Sacchettini Jim J Alley M R K MRK Parish Tanya T

Tuberculosis (Edinburgh, Scotland) 20171107

We identified a series of novel 7-phenyl benzoxaborole compounds with activity against Mycobacterium tuberculosis. Compounds had a range of activity with inhibitory concentrations (IC90) as low as 5.1 μM and no cytotoxicity against eukaryotic cells (IC50 > 50 μM). Compounds were active against intracellular mycobacteria cultured in THP-1 macrophages. We isolated and characterized resistant mutants with mutations in NADH dehydrogenase (Ndh) or the regulatory protein Mce3R. M ...[more]

PMID: 29523334

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