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.