Synthesis, evaluation of biological activity studies of iridium(III) complexes against human gastric carcinoma SGC-7901 cells

Abstract Three new iridium(III) complexes [Ir(ppy)2(DBDPPZ)](PF6) (1), [Ir(bzq)2(DBDPPZ)](PF6) (2) and [Ir(piq)2(DBDPPZ)](PF6) (3) were synthesized and characterization. The cytotoxicity in vitro of the complexes against several cancer cells was evaluated by MTT method. The complexes show high anticancer activity against MDA-DB231, SGC-7901, A549 and HeLa cells. In particular, complexes 1, 2 and 3 exhibit very high cytotoxic effect on SGC-7901 cells with a very low IC50 value of 1.53 ± 0.10, 0.17 ± 0.05 and 0.30 ± 0.03 μM, respectively. The cell colonies formation, intracellular ROS, mitochondrial membrane potential, intracellular Ca2+ levels were investigated under fluorescence microscope. Studies show that the complexes can inhibit cell colonies formation, increase intracellular ROS and Ca2+ levels, induce a decrease in the mitochondrial membrane potential. The apoptosis and cell cycle arrest were also studied by flow cytometry. Additionally, the complexes can regulate the expression of caspase 3 and Bcl-2 family proteins. Taken together, the complexes induce apoptosis in SGC-7901 cells through a ROS-mediated mitochondrial dysfunction pathway.