Antitubercular isoniazid and drug resistance of Mycobacterium tuberculosis--a review.
Isoniazid is one of the most potent drugs available for tuberculosis treatment. As a pro-drug it requires activation, which is performed by catalase/peroxidase. The active principle, whose identity has not yet been determined unambiguously, then acts on at least one target molecule, the enoyl-acyl carrier protein, required for the synthesis of the vital mycolic acids present in the cell wall of the bacterium. Some other targets have been proposed in order to explain the unusual potency of isoniazid; however, the supporting data are still controversial. We thoroughly discuss the action of isoniazid, resistance mechanisms, and the possible active product, which includes an isonicotinic acid-NADH adduct as well as a meta-isomer of NADH. Both structures have been probed positively in a 3D modeling analysis.
Scior
Thomas
T
Department of Pharmacy, Benemérita Universidad Autónoma de Puebla, Puebla, Pue.72570, México.
Meneses Morales
Iván
I
Garcés Eisele
Solón Javier
SJ
Domeyer
David
D
Laufer
Stefan
S
D001426:Bacterial Proteins; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000737:chemistry / Q000187:drug effects / Q000235:genetics; D010544:Peroxidases / Q000378:metabolism / Q000502:physiology*; D014376:Tuberculosis / Q000188:drug therapy* / Q000453:epidemiology; D018088:Tuberculosis, Multidrug-Resistant / Q000235:genetics
D001426:Bacterial Proteins; D010544:Peroxidases; C076136:catalase HPI