A novel carbohydrazide-based ligand (L) and its binuclear Cu(II) complex were successfully synthesized and characterized. Structural analysis confirmed that the Cu(II) complex adopted a monoclinic crystal system with a distorted coordination configuration, in which the multidentate Schiff base ligand chelated and bridged two Cu(II) centers. The in vitro anti-tumor results revealed that the Cu(II) complex exhibited prominent cytotoxicity against five human cancer cell lines with much lower IC50 values than the free ligand, copper chloride and cisplatin. Mechanistic studies demonstrated that the Cu(II) complex significantly increased intracellular ROS and MDA levels, decreased the GSH/GSSG ratio, and reduced ATP content, thereby disrupting cellular redox balance and bioenergetic metabolism. In addition, flow cytometry analysis verified that the complex effectively triggered tumor cell apoptosis. In contrast, free CuCl2 showed almost no anticancer activity, indicating that the synergistic effect between the Schiff base ligand and copper ions contributed to the excellent anti-tumor performance. This work suggests that the prepared binuclear Cu(II) complex can serve as a promising candidate for developing metal-based anticancer agents.
Bai et al. (Thu,) studied this question.