Diseño, síntesis y evaluación biológica de nuevos derivados de selenocianuro como potenciales agentes leishmanicidas

Resum

Leishmaniasis is an ancient protozoan disease affecting about 12 million people with 2 million new cases every year that constitute a serious public health problem. According to the World Health Organization (WHO), leishmaniasis is now endemic in 88 countries, particularly in subtropical and tropical regions. Different studies recognised the trace element selenium as a new defense strategy against Leishmania infection, and also the importance of possible potential interference of selenium derivatives with the redox system of the parasites. Due to the urgent need for innovative drugs and previous work of our research group in organoselenium compounds, we carried out the synthesis and biological evaluation of selenocyanate and diselenide derivatives. All of the compounds prepared during the course of these investigations are stable and they were characterized by spectroscopic methods such as IR and NMR and also by elemental analysis. After that, the compounds have been tested on Leishmania Infantum. The biological evaluation has three stages. At first, the selenocyanate and diselenide compounds have been subjected to in vitro screening against cultured promastigotes of Leishmania infantum. In the second stage, the most active ones have been also tested in axenic amastigotes. In order to establish the selectivity index (SI) their cytotoxic effect was carried out against Jurkat and THP-1 cell lines. Finally, the derivatives, which exhibit the best activity, have been assayed in Leishmania infected macrophages. In summary, we have presented the synthesis of fifty compounds that contain either a selenocyanate or a diselenide moiety. These compounds were evaluated as a potential novel class of antileishmanial agents in the promastigote and amastigote models and their cytotoxic activity against the cancer cell lines Jurkat and THP-1 was investigated. Several compounds combined high potency and low cytotoxicity with SI values higher than those obtained for the reference drugs.