Hydride-induced Meisenheimer complex formation reflects activity of nitro aromatic anti-tuberculosis compounds
Basic Information
ID: ALA4673200
Journal: RSC Med Chem
Title: Hydride-induced Meisenheimer complex formation reflects activity of nitro aromatic anti-tuberculosis compounds
Authors: Liu, Rui, Markley, Lowell, Miller, Patricia A., Franzblau, Scott, Shetye, Gauri, Ma, Rui, Savkova, Karin, Mikusova, Katarina, Lee, Bei Shi, Pethe, Kevin, Moraski, Garrett C., Miller, Marvin J.
Abstract: 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.
CiteXplore: 34046598
DOI: 10.1039/d0md00390e
Patent ID: ┄