ABSTRACT
Leishmaniasis, Chagas disease and sleeping sickness are poverty-related diseases characterized by high morbidity deeply linked to malnutrition, complex humanitarian emergencies and environmental changes that affect vector biology. Trypanosomatids, which are exposed to high amounts of reactive oxygen species, produced by both host macrophage and the protozoa itself, use Trypanothione, a dithiol molecule synthesized starting from two glutathione molecules and one spermidine (Spd), as an efficient detoxification system. Trypanothione Synthetase-amidase (TSA) was demonstrated to be a good candidate to find new and more affordable drugs against neglected diseases caused by trypanosomatids since it is not present in the human host and is essential for the parasite survival. TSA is to date the most promising target: it is a low-abundance, essential enzyme in Leishmania, with no human homologs. TSA inhibitors obtained from high-throughput studies have been demonstrated to be effective against T. brucei.
