Copper(II)-5-chloro-2-hydroxybenzophenone Complexes with N – N Donors: Structural Insights and Antitumor Activity against A2780 Human Ovarian Cancer Cells of a Bathophen Derivative

Five novel heteroleptic copper(II) complexes were synthesized and fully characterized. Unlike previously reported Cu(II)-diimine systems, these complexes incorporate an O,O-chelating 5-chloro-2-hydroxybenzophenone (5-Cl2HBz) ligand, forming cytotoxic compounds active against A2780 (ovarian), A549 (lung), and MCF-7 (breast) cancer cells. The complexes were identified as [Cu(5-Cl2HBz)(phen)(NO3)] (Cu(1)), [Cu(5-Cl2HBz)(bathophen)](NO3)1.5H2O·CH3OH (Cu(2)), [Cu(5-Cl2HBz)(bipy)(NO3)(H2O)] (Cu(3)), [Cu(5-Cl2HBz)(5,5′-bipy)(NO3)] (Cu(4)), and [Cu(5-Cl2HBz)(tert-bipy)(NO3)]·2H2O (Cu(5)), where phen = 1,10-phenanthroline, bathophen = 4,7-diphenyl-1,10-phenanthroline, bipy = 2,2′-bipyridine, 5,5′-bipy = 5,5′-bipyridine, and tert-bipy = 4,4′-bis(tert-butyl)-2,2′-bipyridine. Among the series, complex Cu(2) displayed outstanding potency in A2780 cells (IC50 = 0.24 μM), being 36-fold more potent than cisplatin. This complex significantly affected the cell morphology and colony formation in a concentration-dependent manner. DNA interaction studies revealed that Cu(2) interacts strongly with DNA, as evidenced by viscosity, circular dichroism, and fluorescence measurements. These findings establish Cu(II)-bathophen derivatives as highly promising candidates for the development of copper-based anticancer agents.