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: Malic enzyme, glucose-6-phosphate dehydrogenase, druggability, neglected diseases, NADPH, oxidative
stress defense, parasite growth.
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