Design and biological evaluations of mono- and di-nuclear copper(II) complexes: nuclease activity, cytotoxicity and apoptosis

Abstract Two new mono- and di-nuclear polypyridyl copper complexes [CuL1Br2]2·CH3OH (1) and [Cu2L2Br4]·(DMF)2·H2O (2) were synthesized and characterized by X-ray crystallography, elemental analysis, IR and HR-MS. The structure–activity relationship was comparative studied regarding the nuclease activity and cytotoxicity of the two complexes. According to the results of nuclease activity studies, we found the synergic effect between dinuclear ligand and copper ions as well as the flexibility of the mononuclear ligand and copper ions. The anticancer activities of the complexes towards three human tumor cells lines (HeLa, HepG-2 and SGC-7901) showed that both 1 and 2 exhibt observably inhibitory activity. Especially to HepG-2, IC50 values are obvious less to the clinically-used cisplatin. Cytotoxicity test on human normal cell line HUVEC indicate that both complexes 1 and 2 are less cytotoxic than the control cisplatin. Further in-depth research of complex 2 with HeLa cell line for the anticancer investigation, including colony formation assay, apoptosis evaluation and cell cycle analysis were carried out. The results showed that complex 2 could effectively inhibit the proliferation and induce apoptosis via ROS-triggered pathway of HeLa cells.