According to World Health Organization (WHO), trypanosomiasis and leishmaniasis are the most challenging
among the neglected tropical diseases. Comparative studies between Leishmania spp and Trypanosoma cruzi have been
conducted aiming to find a broad spectrum antiprotozoal agent acting against both parasites. Among the potential molecular
target, Trypanothione reductase (TR) is considered an ideal enzyme since it is involved in the unique thiol-based metabolism
observed in the Trypanosomatidae family and is a validated target for the search of antitrypanosomatidae drugs.
In this review we intend to describe the currently available therapy to treat trypanosomatidae diseases and to highlight important
aspects of trypanothione reductase as a target for the search of new and selective inhibitors, such as tricyclic,
diphenylsulfide, bicyclic and heterocyclic, polyamine, natural product, N-oxide and nitroheterocyclic, aryl β-
aminocarbonyl and α,β-unsaturated carbonyl derivatives.