Cyclometalated iridium(III) dithioformic acid complexes as mitochondria-targeted imaging and anticancer agents

Four neutral cyclometalated iridium(III) (Ir-III) dithioformic acid complexes ([(ppy)(2)Ir((SS)-S-boolean AND)], Ir1-Ir4) were designed and synthesized. Toxicity assay revealed that these complexes showed favorable anticancer activity, especially for human non-small cell lung cancer cells (A549). Ir1 exhibited the best anticancer activity (11.0 +/- 0.4 mu M) was about twice that of cisplatin, meanwhile, which could availably restrain A549 cells migration. Complexes could target mitochondria, induce a decrease in mitochondrial membrane potential (MMP), result in an increase of intracellular reactive oxygen species (ROS) and disruption of the cell cycle, and ultimately generate apoptosis. Western blotting experiment indicated that complexes could inhibit the expression of B cell CLL/lymphoma-2 protein (Bcl-2), induce the expression of BCL2-associated X protein (Bax) and lead to a massive release of Cytochrome C (Cyt-c), which amplified apoptosis signals by activating downstream pathway to promote apoptosis. All these confirmed the existence of mitochondrial anticancer channels for these complexes. Above all, cyclometalated iridium(III) dithioformic acid complexes possess the prospect of becoming a multifunctional cancer therapeutic platform, including mitochondria-targeted imaging, anti-migration, and anticancer agents.

Automated summary

Four neutral cyclometalated iridium(III) dithioformic acid complexes were designed and synthesized, with favorable anticancer activity against non-small cell lung cancer cells through targeting mitochondria and inducing apoptosis.