Promising aryl selenoate derivatives as antileishmanial agents and their effects on gene expression

Leishmaniasis remains one of the main public health problems worldwide, with special incidence in the poorest populations. Selenium and its derivatives can be potent therapeutic options against protozoan parasites. In this work, 17 aryl selenoates were synthesized and screened against three species of Leishmania (Leishmania major, Leishmania amazonensis, and Leishmania infantum). Initial screening in promastigotes showed L. infantum species was more sensitive to selenoderivatives than the others. The lead Se-(2-selenocyanatoethyl) thiophene-2-carboselenoate (16) showed a half-maximal effective concentration of 3.07 µM and a selectivity index > 32.57 against L. infantum promastigotes. It was also the most effective of all 17 compounds, decreasing the infection ratio by 90% in L. infantum-infected macrophages with amastigotes at 10 µM. This aryl selenoate did not produce a hemolytic effect on human red blood cells at the studied doses (10-100 µM). Furthermore, the gene expression of infected murine macrophages related to cell death, the cell cycle, and the selenoprotein synthesis pathway in amastigotes was altered, while no changes were observed in their murine homologs, supporting the specificity of Compound 16 against the parasite. Therefore, this work reveals the possible benefits of selenoate derivatives for the treatment of leishmaniasis.