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Leishmaniasis, is a neglected tropical disease with parasitic origin, which presents two million new cases per year, putting about 350 million people at risk around the world. The number of drugs currently available to fight against leishmaniasis is limited. These drugs are associated with several adverse effects and high treatment costs. Nowadays, the exploration and development of new therapeutic agents using natural products as starting material is considered as a powerful strategy in medicinal chemistry. In this work, we present the molecular optimization of a coumarin derivative (1) that had showed potential leishmanicidal action, but limited water solubility and high cytotoxicity. The structural modifications were oriented to transform the methoxy group into hydroxy, to increase the polarity of the molecule and the evaluation of the influence of the nitro group on the cytotoxicity. The three derivatives (2-4) obtained were evaluated on promastigotes of Leishmania amazonensis, and the cytotoxicity evaluation was performed on murine peritoneal macrophages
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