Hydride-induced Meisenheimer complex formation reflects activity of nitro aromatic anti-tuberculosis compounds

The formation efficiency of hydride-induced Meisenheimer complexes of nitroaromatic compounds is consistent with their anti-TB activities exemplied by MDL860 and benzothiazol N -oxide (BTO) analogs. Herein we report that nitro cyano phenoxybenzenes (MDL860 and analogs) reacted slowly and incompletel...

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Published in:MedChemComm 2021-01, Vol.12 (1), p.62-72
Main Authors: Liu, Rui, Markley, Lowell, Miller, Patricia A, Franzblau, Scott, Shetye, Gauri, Ma, Rui, Savková, Karin, Mikušová, Katarína, Lee, Bei Shi, Pethe, Kevin, Moraski, Garrett C, Miller, Marvin J
Format: Article
Language:English
Subjects:
Analogs
Aromatic compounds
Chemistry
Complex formation
Derivatives
Hydrides
NMR
Nuclear magnetic resonance
Radiolabelling
Tuberculosis
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Summary:The formation efficiency of hydride-induced Meisenheimer complexes of nitroaromatic compounds is consistent with their anti-TB activities exemplied by MDL860 and benzothiazol N -oxide (BTO) analogs. Herein we report that nitro cyano phenoxybenzenes (MDL860 and analogs) reacted slowly and incompletely which reflected their moderate anti-TB activity, in contrast to the instantaneous reaction of BTO derivatives to quantitatively generate Meisenheimer complexes which corresponded to their enhanced anti-TB activity. These results were corroborated by mycobacterial and radiolabelling studies that confirmed inhibition of the DprE1 enzyme by BTO derivatives but not MDL860 analogs. The formation efficiency of hydride-induced Meisenheimer complexes of nitroaromatic compounds is consistent with their anti-TB activities exemplied by MDL860 and benzothiazol N -oxide (BTO) analogs.
ISSN:2632-8682
2040-2503
2632-8682
2040-2511
DOI:10.1039/d0md00390e