3,5-Dimethyl-4-isoxazoyl selenocyanate as promising agent for the treatment of Leishmania infantum-infected mice.

Abstract

Compounds 1 and 2 (selenocyanate and diselenide derivatives, respectively) were evaluated for their potential use in vivo against visceral leishmaniasis (VL). Both entities showed low cytoxicity in vitro in Vero and Caco-2 cell lines. However, the compounds were not suitable for their oral administration, since they exhibited poor values of intestinal permeability in vitro. Microsomal stability assays did not show any metabolite for compound 1 after 120 min, whereas 2 was highly metabolized by the enzyme CYP450. Thus, the in vivo efficacy of compound 1 was assessed in a murine model of L. infantum VL. The daily i.v. administration of 1 mg/kg of compound 1 during 5 consecutive days reduced parasite load in liver, spleen and bone marrow (99.2%, 91.7% and 61.4%, respectively) compared to non-treated mice. To the best of our knowledge, this is the first time that a selenium compound has been tested in vivo against VL. Thus, this work evidences the possible usefulness of selenocyanate derivatives for the treatment of this disease.

• Authors: Verónica Alcolea, Esther Moreno, Mikel Etxebeste-Mitxeltorena, Iñigo Navarro-Blasco, Elena González-Peñas, Antonio Jiménez-Ruiz, Juan Manuel Irache, Carmen Sanmartín, Socorro Espuelas
• Journal: Acta tropica (Acta Trop) Vol. 215 Pg. 105801 (Mar 2021) ISSN: 1873-6254 [Electronic] Netherlands
• PMID: 33352169 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier B.V.

Chemical References

• Cyanates
• Selenium Compounds
• selenocyanic acid

Topics

• Animals
• Cells, Cultured
• Cyanates (therapeutic use)
• Female
• Humans
• Leishmania infantum
• Leishmaniasis, Visceral (drug therapy)
• Mice
• Mice, Inbred BALB C
• Rats
• Rats, Wistar
• Selenium Compounds (therapeutic use)