RESUMEN
Several benzocyclobutacarbazol derivatives were synthesized and evaluated for their potential cytotoxic properties. A number of these compounds exhibited significant antiproliferative activity with concomitant interaction with the cell cycle and represent a new class of potential anticancer agents.
Asunto(s)
Antineoplásicos/síntesis química , Antineoplásicos/farmacología , Carbazoles/síntesis química , Carbazoles/farmacología , Ciclobutanos/síntesis química , Ciclobutanos/farmacología , Animales , Carbazoles/química , Ciclobutanos/química , Ensayos de Selección de Medicamentos Antitumorales , Ratones , Células Tumorales CultivadasRESUMEN
Series of indole-2-carboxamide and cycloalkeno[1,2-b]indole derivatives were synthesized and evaluated in order to determine the necessary structural requirements for a high inhibition of human LDL copper-induced peroxidation. Various modulations were systematically performed on the indole and cycloalkeno[1,2-b]indole nuclei as well as on the carboxamide moiety. The best compounds (3c, 3e, 7c, 7f, 7h, 7g, and 7o) are between 5 and 30 times more active than probucol itself. Two of these compounds (3c and 7o) were selected for complementary in vitro and in vivo investigations, which have shown additional properties of interest for the treatment and the prevention of atherosclerosis injuries. Compound 3c was found to have some antiinflammatory properties while compound 7o was proved to protect endothelial cells from the direct cytotoxicity of oxidized LDL with some additional calcium channel blocking properties.