Chemotherapy treatment of leishmaniasis is based on the use of pentavalent antimonials, but these drugs present low efficacy and high toxicity. In the search for new antileishmanial agents, essential oils (EOs) from four Croton species (C. argyrophylloides, C. jacobinensis, C. nepetifolius and C. sincorensis) were evaluated against Leishmania infantum chagasi, L. amazonensis and L. braziliensis. EOs were analyzed by gas chromatography combined with mass spectrometry. Spathulenol, β-caryophyllene, β-caryophyllene oxide, 1,8-cineole and methyl eugenol were the major constituents. The evaluation of antioxidant activity by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) method showed that all EOs have moderate antioxidant activity. All oils were similarly active against L. i. chagasi, and C. nepetifolius EO showed the best result against L. amazonensis, with median inhibitory concentrations (IC50) of 9.87 μg mL-1, similar to amphotericin B (IC50 = 7.38 μg mL-1). The oils presented low cytotoxicity in macrophages. The in silico analysis revealed that spathulenol and 1,8-cineole were active against the enzyme Leishmania infantum trypanothione reductase (LiTR), showing excellent interaction energies, making them promising agents for leishmaniasis control.
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