Selenocyanates and diselenides: A new class of potent antileishmanial agents

Thirty five selenocyanate and diselenide compounds were subjected to in vitro screening against Leishmania infantum promastigotes and the most active ones were also tested in an axenic amastigote model. In order to establish the selectivity indexes (SI) the cytotoxic effect of each compound was also assayed against Jurkat and THP-1 cell lines.Thirteen derivatives exhibit better IC50 values than miltefosine and edelfosine. Bis(4-aminophenyl)diselenide exhibits the best activity when assayed in infected macrophages and one of the lowest cytotoxic activities against the human cell lines tested, with SI values of 32 and 24 against Jurkat and THP-1 cells, respectively. This compound thus represents a new lead for further studies aimed at establishing its mechanism of action.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Thirty five selenocyanates and diselenides were synthesized. ► Compounds were tested as leishmanicidal and cytotoxic agents and SI was determined. ► Diselenide derivatives showed better biological profile than selenocyanates. ► Bis(4-aminophenyl)diselenide was 4-fold more potent than standard miltefosine.