Synthesis and evaluation of substrate analogue inhibitors of trypanothione reductase.
J Enzyme Inhib Med Chem
; 27(6): 784-94, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22085139
ABSTRACT
Trypanothione reductase (TR) is found in the trypanosomatid parasites, where it catalyses the NADPH-dependent reduction of the glutathione analogue, trypanothione, and is a key player in the parasite's defenses against oxidative stress. TR is a promising target for the development of antitrypanosomal drugs; here, we report our synthesis and evaluation of compounds 3-5 as low micromolar Trypanosoma cruzi TR inhibitors. Although 4 and 5 were designed as potential irreversible inhibitors, these compounds, as well as 3, displayed reversible competitive inhibition. Compound 3 proved to be the most potent inhibitor, with a K(i) = 2 µM.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Tripanocidas
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Trypanosoma cruzi
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Espermidina
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Glutatión
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NADH NADPH Oxidorreductasas
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NADP
Idioma:
En
Revista:
J Enzyme Inhib Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2012
Tipo del documento:
Article