2. Academic Validation
  3. Pre-clinical evidences of the antileishmanial effects of diselenides and selenocyanates

Pre-clinical evidences of the antileishmanial effects of diselenides and selenocyanates

  • Bioorg Med Chem Lett. 2020 Sep 1;30(17):127371. doi: 10.1016/j.bmcl.2020.127371.
Pablo Garnica 1,  Mikel Etxebeste-Mitxeltorena 2,  Daniel Plano 2,  Esther Moreno 2,  Socorro Espuelas 2,  Juan Antonio Palop 1,  Antonio Jiménez-Ruiz 3,  Carmen Sanmartín 4
Affiliations

Affiliations

  • 1 University of Navarra, School of Pharmacy and Nutrition, Department of Pharmaceutical Technology and Chemistry, Irunlarrea 1, 31008 Pamplona, Spain.
  • 2 University of Navarra, School of Pharmacy and Nutrition, Department of Pharmaceutical Technology and Chemistry, Irunlarrea 1, 31008 Pamplona, Spain; Institute of Tropical Health, University of Navarra, Pamplona, Spain.
  • 3 Department of Biochemistry and Molecular Biology, Universidad de Alcalá, Carretera Madrid-Barcelona km 33,600, E-28871 Alcalá de Henares, Madrid, Spain.
  • 4 University of Navarra, School of Pharmacy and Nutrition, Department of Pharmaceutical Technology and Chemistry, Irunlarrea 1, 31008 Pamplona, Spain; Institute of Tropical Health, University of Navarra, Pamplona, Spain. Electronic address: sanmartin@unav.es.
PMID: 32738977 DOI: 10.1016/j.bmcl.2020.127371
Abstract

A series of thirty-one selenocompounds covering a wide chemical space was assessed for in vitro leishmanicidal activities against Leishmania infantum amastigotes. The cytotoxicity of those compounds was also evaluated on human THP-1 cells. Interestingly most tested derivatives were active in the low micromolar range and seven of them (A.I.3, A.I.7, B.I.1, B.I.2, C.I.7 C.I.8 and C.II.8) stood out for selectivity indexes higher than the ones exhibited by reference compounds mitelfosine and edelfosine. These leader compounds were evaluated against infected macrophages and their trypanothione reductase (TryR) inhibition potency was measured to further approach the mechanism by which they caused their action. Among them diselenide tested structures were pointed out for their ability to reduce Infection rates. Three of the leader compounds inhibited TryR effectively, therefore this Enzyme may be implicated in the mechanism of action by which these compounds cause their leishmanicidal effect.

Keywords

Diselenides; Leishmanicidal agents; Selenocompounds; Selenocyanates.

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