In vitro and in vivo effects of digoxin derivatives on promastigotes and amastigotes of Leishmania infantum

Abstract

Leishmania infantum is responsible for visceral leishmaniasis, the most severe form of the disease. The treatments currently used are pentavalent antimonials and amphotericin B, but they present serious side effects and resistant species that already exist. Therefore, it is necessary to find new compounds to avoid those acute problems. In vitro, this study evaluated the effects of fifteen digoxin derivative compounds on promastigotes and two of these compounds on amastigotes of L. infantum. We also assess the impact of these compounds on mitochondrial metabolism. The results showed that two of the fifteen compounds tested showed a high anti-Leishmania effect. Compounds 3 and 15 showed no toxicity across the cell lines RAW 264.7. Compound 15 inhibited macrophage infection and reduced the number of amastigotes. The two compounds showed a reduction in oxygen consumption by promastigotes. In this way, compounds 3 and 15 appear to be promising anti-leishmanial. Therefore, we checked both compounds in vivo also evaluating the toxicity by measuring ALT, AST, urea, and creatinine. Our results may contribute in the future to the development and application of new anti-Leishmania drugs.