An inorganic iron complex that inhibits wild-type and an isoniazid-resistant mutant 2-trans-enoyl-ACP (CoA) reductase from Mycobacterium tuberculosis.
The in vitro kinetics of inactivation of both wild-type and I21V InhA enzymes by [FeII(CN)5(INH)]3- indicate that this process requires no activation by KatG, and no need for the presence of NADH. This inorganic complex may represent a new class of lead compounds to the development of anti-tubercular agents aiming at inhibition of a validated target.
Oliveira
Jaim S
JS
Universidade Federal do Rio Grande do Sul, Departamento de Biologia Molecular e Biotecnologia, Av. Bento Gonçalves 9500, Porto Alegre, RS 91501-970, Brazil. labasso@dna.cbiot.ufrgs.br
Sousa
Eduardo H S
EH
Basso
Luiz A
LA
Palaci
Moisés
M
Dietze
Reynaldo
R
Santos
Diógenes S
DS
Moreira
Icaro S
IS
D024881:Drug Resistance, Bacterial; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D007501:Iron / Q000494:pharmacology*; D007538:Isoniazid / Q000494:pharmacology*; D015394:Molecular Structure; D009154:Mutation / Q000235:genetics*; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
D009243:NAD; D007501:Iron; D010088:Oxidoreductases; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH); D007538:Isoniazid