Trypanothione metabolism as drug target for trypanosomatids

PIÑEYRO, MARÍA DOLORES; ARIAS, DIEGO G.; PARODI-TALICE, ADRIANA; GUERRERO, SERGIO A.; ROBELLO, CARLOS

CURRENT PHARMACEUTICAL DESIGN.

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2021 vol. 27 p. 1834 - 1846

1381-6128

Trypanosomatids presents a unique trypanothionebased redox system, which is the main responsible for maintaining the redoxbalance. The system contains different redox cascades, where both NADPH as a sourceof electrons, trypanothione and tryparedoxins, play a central role intransferring reducing power to different enzymes, such as 2-Cys peroxiredoxins,non-selenium glutathione peroxidases and ascorbate peroxidases. These enzymeshave different substrate specificity, catalytic efficiency, physiologicalreductants, and subcellular localization. It also transfers reductionequivalents to other enzymes, such as glutaredoxins and methionine sulfoxidereductases. There is sufficient evidence that this complex system is essentialfor parasite survival and infection. The combination of molecular biology,bioinformatics, genomics, and structural biology is fundamental since theknowledge of unique features of the trypanothione dependent system will providetools for rational drug design, in order to develop new treatments for diseasescaused by these parasites.