Studies on the Mechanism of Action of Isoniazid and Ethionamide in the Chemotherapy of Tuberculosis

The inactivation of the enoyl-reductase InhA from Mycobacterium tuberculosis by reactive intermediates formed during the oxidn. of isoniazid and ethionamide was studied. Both drugs can generate electrophilic intermediates capable of reacting with a nucleophilic group of InhA, leading to its inactivation. After inactivation of InhA by isoniazid, one mol. of isoniazid per InhA is covalently bound to the enzyme. Mapping studies suggest that Cys243 is the residue modified in the course of the inactivation. [on SciFinder (R)]

Published in:
Journal of the American Chemical Society, 117, 17, 5009-10

 Record created 2006-02-27, last modified 2018-03-17

Rate this document:

Rate this document:
(Not yet reviewed)