Novel platinum(II) and palladium(II) complexes with N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-(bis(2-benzimidazolylmethyl)amino)acetamide as potential anticancer agents.

Novel platinum(II) and palladium(II) complexes, [PtLCl]Cl (1) and [PdLCl]Cl (2) (where L = N-(4-(benzo[d]oxazol-2-yl)phenyl)-2-(bis(2-benzimidazolylmethyl)amino)acetamide), were synthesized and characterized. The binding experiments of the complexes with CT-DNA illustrated that both 1 and 2 could strongly bind to DNA in a dual binding mode, i.e., the groove-binding mode plus monofunctional platination of the metal moiety, and induce changes in the tertiary structure of DNA, where the DNA-binding affinity of 2 was higher than that of 1. The in vitro cytotoxicity activity tests showed that the two complexes displayed effective cytotoxic activity against all the tested cancer cell lines, especially human breast cancer MCF-7, human colon cancer HCT-116, and human cervical cancer HeLa cells. 1 was more sensitive to HCT-116 and MCF-7, and 2 was more sensitive to HeLa and MCF-7. Both 1 and 2 exhibited comparable activity against MCF-7 to that of cisplatin but were less toxic to human normal breast epithelial MCF-10A cell lines. Moreover, flow cytometry analysis demonstrated that the two complexes arrested MCF-7 cells mainly at the G2/M phase, induced mitochondrial membrane depolarization, increased ROS generation, and triggered obvious cell apoptosis. Thus, the present study features the two novel platinum(II) and palladium(II) complexes as promising candidates for chemotherapeutic agents.