From Zn to Mn: the study of novel manganese-binding groups in the search for new drugs against tuberculosis.
Chem Biol Drug Des
; 77(2): 117-23, 2011 Feb.
Article
en En
| MEDLINE
| ID: mdl-21266015
ABSTRACT
In most eubacteria, apicomplexans, and most plants, including the causal agents for diseases such as malaria, leprosy, and tuberculosis, the methylerythritol phosphate pathway is the route for the biosynthesis of the C(5) precursors to the essential isoprenoid class of compounds. Owing to their absence in humans, the enzymes of the methylerythritol phosphate pathway have become attractive targets for drug discovery. This work investigates a new class of inhibitors against the second enzyme of the pathway, 1-deoxy-D-xylulose 5-phosphate reductoisomerase. Inhibition of this enzyme may involve the chelation of a crucial active site Mn ion, and the metal-chelating moieties studied here have previously been shown to be successful in application to the zinc-dependent metalloproteinases. Quantum mechanics and docking calculations presented in this work suggest the transferability of these metal-chelating compounds to Mn-containing 1-deoxy-D-xylulose 5-phosphate reductoisomerase enzyme, as a promising starting point to the development of potent inhibitors.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Oxidorreductasas
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Tuberculosis
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Zinc
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Isomerasas Aldosa-Cetosa
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Inhibidores Enzimáticos
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Manganeso
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Complejos Multienzimáticos
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Antituberculosos
Límite:
Humans
Idioma:
En
Año:
2011
Tipo del documento:
Article