The mechanism of action of isoniazid. a chemical model of activation
Bernadou, J.; Nguyen, M.; Meunier, B.
Annales Pharmaceutiques Francaises 59(5): 331-337
2001
ISSN/ISBN: 0003-4509 PMID: 11787427 Document Number: 532275
The antituberculosis drug isoniazid (INH) is quickly oxidized by stoichiometric amounts of manganese(III)-pyrophosphate. In the presence of the nicotinamide coenzyme, the INH oxidation produced the formation of INH-NAD(H) adducts which are potential competitive inhibitors of the enoyl-acyl carrier protein reductase InhA, an INH target in the biosynthetic pathway for mycolic acids. Manganese(III)-pyrophosphate is an efficient alternative oxidant to mimick the activity of the Mycobacterium tuberculosis KatG catalase-peroxidase and will be useful for further mechanistic studies of INH activation and for structural investigations on reactive INH species and resulting InhA inhibitors.