Leishmaniasis is one of the world's most
neglected diseases, and it has a worldwide prevalence of 12 million. There are no effective human
vaccines for its prevention, and treatment is hampered by outdated drugs. Therefore, research aiming at the development of new therapeutic tools to fight
leishmaniasis remains a crucial goal today. With this purpose in mind, we present 20 arylaminoketone derivatives with a very interesting in vitro and in vivo efficacy against Trypanosoma cruzi that have now been studied against promastigote and amastigote forms of Leishmania infantum, Leishmania donovani and Leishmania braziliensis strains. Six out of the 20
Mannich base-type derivatives showed Selectivity Index between 39 and 2337 times higher in the amastigote form than the reference drug
glucantime. These six derivatives affected the parasite infectivity rates; the result was lower parasite infectivity rates than
glucantime tested at an IC25 dose. In addition, these derivatives were substantially more active against the three Leishmania species tested than
glucantime. The mechanism of action of these compounds has been studied, showing a greater alteration in
glucose catabolism and leading to greater levels of
iron superoxide dismutase inhibition. These molecules could be potential candidates for
leishmaniasis chemotherapy.