Diseño, síntesis y evaluación biológica de nuevos derivados diseleniuro con actividad antitumoral y leishmanicida

Résumé

ents with high cytotoxic activities. In this study, we have synthesized a novel series of symmetric aromatic ureas, thioureas and selenoureas containing diphenyldiselenide entity. Thermal stability analysis of these derivatives by thermogravimetry, differential scanning calorimetry and mass spectrometry revealed that ureas and selenoureas are more stable than thioureas. Most of the compounds displayed high antiproliferative activity against a panel of human cancer cell lines. The derivative DPDS 2 presented the lowest GI50 value whereas DPDS 6 was the compound with the highest selectivity index for cancer cells. Biological evaluation demonstrates that DPDS 2 arrest at the G0/G1 phase, and induced apoptosis-mediated cell death in lymphoblastic leukemia CCRF-CEM cells. On the other hand, derivative DPDS 6 induced G2/M arrest and autophagy-mediated cell death in HTB-54 lung cancer cells. Moreover the in vitro leishmanicidal activities against Leishmania infantum axenic amastigotes along with their selectivity in human THP-1 cells were also determined. Thirteen of the compounds analyzed displayed antileishmanicidal activity with IC50 values lower than the reference drug mitelfosine. Derivatives 9, 11, 42 and 47 showed high selectivity index for Leishmania, but only the compound 47 inhibited trypanothione reductase. These results highlight the anticancer and leishmanicidal activity of these derivatives and may serve as the basis for future studies examining the clinical value of these reagents.