New platinum(II)-based DNA intercalator: Synthesis, characterization and anticancer activity

Platinum agents with different action mechanisms from current platinum drugs can be effective candidates overcoming the resistance of platinum-based drugs. Platinum(II)-based DNA intercalators are potent candidate which act through mechanisms distinct from cisplatin. Here, we describe the synthesis and characterize of two platinum (II)-based DNA intercalators containing 2-substituted quinoline derivatives as ligands. In comparison to cisplatin, Qui-Pt-2 exhibited a greater in vitro cytotoxicity overall, and lower resistance factor than cisplatin against SK-OV-3/DDP (1.29 to 3.32). Mechanistic experiments indicate that Qui-Pt-2 can induce the apoptotic death of Bel-7404 cancer cells through intrinsic and extrinsic pathways involved ATP depletion, loss of mitochondrial membrane potential. To the best of our knowledge, Qui-Pt-2 is the first platinum(B)-based DNA intercalator which can simultaneously activate the intrinsic and extrinsic pathways of apoptosis, therefore, Qui-Pt-2 is a promising model compound for anticancer drug development.