Leishmaniasis is endemic in 98 countries, with about 12 million people infected worldwide. Visceral leishmaniasis (VL), given its high incidence and mortality, is considered by the World Health Organization as one of the most important diseases nowadays. Leishmaniasis treatment relies on a limited therapeutic arsenal, with toxic drugs administered by the parenteral route such as pentavalent antimonials, amphotericin B and pentamidine. The toxicity, high cost and route of administration of these drugs, coupled with parasite resistance to antimonials in some regions, indicate that the discovery of new alternatives for leishmaniasis treatment is essential, as new drugs or new chemotherapy regimens using drug combinations. The leishmanicidal activity of tamoxifen was recently described in experimental models of leishmaniasis. Therefore, the aim of this project is to characterize the antileishmanial activity of the Selective Estrogen Receptor Modulators (SERMs) raloxifene and tamoxifen, alone or in combinations of drugs on LV models. For that purpose, a model of LV using luminescent parasites will be implemented. In parallel, this study focuses on understanding the leishmanicidal mechanism of action of these compounds. Through this project we are looking to identify new drug candidates or combination therapy schemes for VL treatment. We believe that data obtained in this project might provide the basis for a clinical trial design, given that tamoxifen and raloxifene have well established clinical safety profiles.
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