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. Mutations suggest that Ndh may be the target of this series.
- Bacterial ProteinsBoron CompoundsBridged Bicyclo Compounds, HeterocyclicDose-Response Relationship, DrugDrug Resistance, BacterialHumansMicrobial Sensitivity TestsMutationMycobacterium TuberculosisNadh DehydrogenaseThp-1 Cells