Study of new drug candidates for neglected protozoan diseases

Abstract

Neglected protozoan diseases as Leishmaniasis and Chagas Disease affect more than 20 million people, mainly in developing countries. Considering the rstricted therapeutic arsenal, toxic and inefficient, new treatments are urgently needed. In the search for new compounds, natural metabolites represent a promising source of pharmaceutical prototypes. The present proposal aims to identify new natural compounds of marine microbial origin and metabolites from Brazilian plants, whith potent in vitro activity against Leishmania (L.) infantum and Trypanosoma cruzi. The metabolites will be isolated using bio-guided fractionation studies, using different chromatographic techniques. The potency of the compounds will be evaluated using phenotypic in vitro assays of intracellular amastigotes of Leishmania infantum and Trypanosoma cruzi. Cytotoxicity studies will be used to obtain the selectivity index. The mechanisms of antiparasitic action of the most promising compounds will be studied using techniques in flow cytometry, spectrofluorimetry and transmission electron microscopy and mass spectrometry in order to determine changes in bioenergetic metabolism, plasma membrane and in lipid metabolism. The chemical structure of active compounds will be determined using spectroscopic and spectroscopic techniques. Considering the need for new drugs for neglected protozoan diseases, this project may contribute to the selection of new molecules of natural origin that can be used as future pharmaceutical prototypes. (AU)