Hydride-induced Meisenheimer complex formation reflects activity of nitro aromatic anti-tuberculosis compounds
| Autor: | Kevin Pethe, Karin Savková, Lowell D. Markley, Marvin J. Miller, Rui Ma, Gauri Shetye, Garrett C. Moraski, Bei Shi Lee, Katarína Mikušová, Patricia A. Miller, Rui Liu, Scott G. Franzblau |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
chemistry.chemical_classification 0303 health sciences 010405 organic chemistry Chemistry Hydride Organic Chemistry Pharmaceutical Science 01 natural sciences Biochemistry Medicinal chemistry Meisenheimer complex 0104 chemical sciences 03 medical and health sciences Enzyme Anti tuberculosis Drug Discovery Nitro Molecular Medicine 030304 developmental biology |
| Zdroj: | RSC Med Chem |
| ISSN: | 2632-8682 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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