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.

KEYWORDS:

• Leishmania
• L. infantum
• leishmaniasis
• digoxin
• digitalis

Acknowledgments

The authors thank Dr. Thomas Goreau (CEO of Global Coral Reef Alliance) and Dr. Daniel Clemente de Moares (IMPG – UFRJ) for critical review of this manuscript. The authors also like to thank Dr. Alane Beatriz Vermelho, Dr. Eliana Barreto-Bergter and Dr. Lucy Seldin for the valuable financial support.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was financed by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brazil (CAPES) – Finance Code 001, FAPEMIG APQ 01915–22 and APQ 00855-19.