Identification of antimalarials with anti-gametocytocidal potentials

Abstract

Malaria is the parasitic disease that most affects populations in the world, causing high morbity and mortality, besides great financial costs to the endemic country. Essential strategy for the disease control, chemotherapy is hampered by the widespread resistance of parasites to the antimalarials that target their asexual forms. With the exception of primaquine, which causes severe adverse effects, these antimalarials are not active against the sexual forms of the parasite. Given the high frequency of genetic recombination during the sexual phase of the cycle, along with the need for a primaquine surrogate, the identification and development of new transmission-blocking drugs become imperative. An obstacle is the lack of in vitro experimental models that speed up the identification of gametocytocidal antimalarial candidates. This project aims at (i) the identification of inducers of Plasmodium falciparum gametocytogenesis, obtained from a large library synthesized by collaborating chemists; (ii) the development of a robust in vitro gametocyte culture, based on promising previous results; (iii) the evaluation of the gametocytocidal activity of compounds, made available by the partnership composed by great pharmaceutical companies termed "Malaria box", with reported activity against asexual stages. An additional objective is to evaluate the activity of compounds, synthesized by collaborating chemists from several national institutions, against asexual blood forms of multiresistant strains of P. falciparum, in the search for new blood-schizonticidal antimalarials. The approval of this project will aid malaria control in the world, enabling its elimination and eradication.