Aquation Is a Crucial Activation Step for Anticancer Action of Ruthenium(II) Polypyridyl Complexes to Trigger Cancer Cell Apoptosis

摘要: Aquation has been proposed as crucial chemical action step for ruthenium (Ru) complexes, but its effects on the mechanisms remain elusive. Herein, we have demonstrated aquation process of a potent Ru polypyridyl complex (RuBmp=[Ru(II) (bmbp)(phen)Cl]ClO4 , bmbp=2,6-bis(6-methylbenzimidazol-2-yl) pyridine, phen=phenanthroline) with chloride ligand, and revealed that RuBmp effectively enhanced hydrophilicity cellular uptake, thus significantly increasing anticancer efficacy. The products (H-RuBmp=[Ru(II) [Ru(II) (bmbp)(phen)(H2 O)]ClO4 bmbp) exhibited much higher apoptosis-inducing ability than intact complex, involvement caspase activation, mitochondria dysfunction, interaction cell membrane death receptors. H-RuBmp potency induced levels ROS overproduction in cancer cells to regulate AKT, MAPK, p53 signaling pathways. Taken together, this study could provide useful information fine-tuning rational design next-generation metal medicines.