RESUMO
Cyclometalated iridium(III) complexes represent a promising approach to developing new anticancer metallodrugs. In this work, three phosphorescent cyclometalated iridium(III) complexes Ir1-Ir3 have been explored as mitochondria-targeted anticancer agents. All three complexes display higher antiproliferative activity than cisplatin against the cancer cells screened, and with the IC50 values ranging from 0.23 to 5.6 µM. Colocalization studies showed that these complexes are mainly localized in the mitochondria. Mechanism studies show that these complexes exert their anticancer efficacy through initiating a series of events related to mitochondrial dysfunction, including depolarization of mitochondrial membrane potential (MMP), elevation of intracellular reactive oxygen species (ROS) levels, and induction of apoptosis. Mitochondria-targted cyclometalated iridium complexes induce apoptosis through depolarized mitochondria, elevation of intracellular ROS and activated caspase.
Assuntos
Antineoplásicos/farmacologia , Complexos de Coordenação/farmacologia , Irídio/farmacologia , Mitocôndrias/efeitos dos fármacos , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Irídio/química , Mitocôndrias/metabolismo , Estrutura Molecular , Espécies Reativas de Oxigênio/análise , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-AtividadeRESUMO
A series of new 1-(carbamoylmethyl)-2-aryl-3,1-benzoxazines were prepared in moderate to good yields by BF3·OEt2-catalyzed reactions of aromatic aldehydes with 2-(N-substituted carbamoylmethylamino)benzyl alcohols. The structures of the target compounds were confirmed by IR, ¹H-NMR, 13C-NMR, and elemental analyses. The fungicidal activities of the target compounds against plant fungi were preliminarily evaluated, and some of them exhibited good activity.
