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Leishmaniasis is a complex of parasitic diseases caused by protozoa of the genus Leishmania. It can compromise the skin, viscera and mucous membranes depending on the species that attacks the host. The main measure of disease control is treatment, but it has several limitations, such as side effects, selection of resistant parasites and reduced efficacy. With this, the World Health Organization encourages the search for new drugs and natural products that can minimize the limitations of existing treatment. The objectives of this study were to prepare ethanolic extracts from plants of the genus Handroanthus and extract lapachol to characterize and evaluate their in vitro and in vivo efficacy against Leishmania amazonensis and L. infantum and to determine the cytotoxicity of lapachol and extracts in cells HepG2. Through the branches collected from Handroanthus species, a chromatographic analysis of each species was performed, where the presence of quinones was observed, and the test done with Na2CO3 2% on a touch plate showed that only H. serratifolius was positive for lapachol. From this the ethanolic extracts were prepared and the chemical extraction of lapachol was carried out. By the methods of TLC and HPLC the phytochemical profile of the samples collected was characterized. Lapachol extracted from H. serratifolius showed a cytotoxicity in HepG2 cells, evaluated by the MTT colorimetric method, of 826.66 ± 82.67 μg / mL. The same demonstrated activity in both the in vitro and in vivo assays, having an IC50 of 19.38 ± 2.21 μg/mL for L. amazonensis and 32.96 ± 8.02 μg/mL for L. infantum in the Resazurin and parasite load reduction of 75.3%. With intracellular amastigotes there was reduction of infection in relation to the control. Lapachol was able to induce a mean reduction of the parasitic load (75.3%) in a murine model of tegumentary leishmaniasis. These results reinforce the therapeutic potential of lapachol and open new perspectives for the treatment of leishmaniasis.

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