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

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.

SUBMITTER: Liu R

PROVIDER: S-EPMC8130608 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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

Liu Rui R Markley Lowell L Miller Patricia A PA Franzblau Scott S Shetye Gauri G Ma Rui R Savková Karin K Mikušová Katarína K Lee Bei Shi BS Pethe Kevin K Moraski Garrett C GC Miller Marvin J MJ

RSC medicinal chemistry 20210104 1

The formation efficiency of hydride-induced Meisenheimer complexes of nitroaromatic compounds is consistent with their anti-TB activities exemplied by MDL860 and benzothiazol <i>N</i>-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 enha ...[more]

PMID: 34046598

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