Protein-kinase inhibitors as potential leishmanicidal drugs

Leishmaniasis is a parasitic vector-borne disease caused by more than 20 species from the genus Leishmania, a protozoan with two distinct morphological forms throughout its life cycle adapted to each one of its two hosts: the promastigote (extracellular) in the invertebrate vector, and the amastigote (intracellular) in the vertebrate host. Although it is mostly a zoonotic disease, anthroponotic transmission occurs in endemic areas with high human density. Moreover, its prevalence increased in the last years due to several factors including an increase in worldwide travelling as well as an increase in the geographical distribution of the phlebotomine vector due to global warming. Despite the efforts to develop human vaccines, the main treatment against leishmaniasis relies on chemotherapy. However, all the current clinical drugs available have drawbacks due to toxicity, high-cost and/or resistance. Two approaches are leading the search for new pharmacological treatments: combination therapy using current drugs available, and searching for new compounds with a leishmanicidal potential through three major strategies: drug repurposing, phenotypic screenings and target-based screenings..