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Curr Med Chem. 2018 Oct 9. doi: 10.2174/0929867325666181009152844. [Epub ahead of print]

NADPH producing enzymes as promising drug targets for Chagas Disease.

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1
Brazilian Bioscience National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas-SP. Brazil.

Abstract

Reduced nicotinamide adenine dinucleotide phosphate (NADPH) is a cofactor used in different anabolic reactions, such as lipid and nucleic acid synthesis, and for oxidative stress defense. NADPH is essential for parasite growth and viability. In trypanosomatid parasites, NADPH is supplied by the oxidative branch of the pentose phosphate pathway and by enzymes associated with the citric acid cycle. The present article will review recent achievements that suggest glucose-6-phosphate dehydrogenase and the cytosolic isoform of the malic enzyme as promising drug targets for the discovery of new drugs against Trypanosoma cruzi and T. brucei. Topics involving an alternative strategy in accelerating T. cruzi drug-target validation and the concept of drug-target classification will also be revisited.

KEYWORDS:

Druggability; Glucose-6-phosphate dehydrogenase; Malic enzyme; Neglected diseases.

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