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

Résumé

A series of novel selenium-containing compounds with potential antitumoral and/or leishmanicidal activity has been synthesized and evaluated in this work. Since the chemical form of selenium (Se) is determinant for its biological activity, we have explored the effects of different Se-containing substituents. To further increase the activity of the novel compounds, the different Se-containing substituents have been incorporated into different heterocyclic scaffolds which demonstrated antitumoral and antiparasitic activity. In addition, some of their sulfur analogs were also evaluated to compare the activity between these two chalcogens. The novel derivatives containing the functionalities selenol, methylseleno, selenocyanate and carbamimidoselenoate have been tested against a panel of several human cancer cell lines and those with selenocyanate and diselenide, against Leishmania infantum amastigotes. The most active and selective molecules in each case have been selected for further biological studies to elucidate their possible mechanism of action. Furthermore, preclinical studies with the lead compounds in leishmaniasis have been carried out. In addition, the thermal stability and the presence of polymorphism, two properties which might affect the biological activity, have been also evaluated in some of the new derivatives.