Copper(II)-5-chloro-2-hydroxybenzophenone Complexes with <i>N</i> – <i>N</i> 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-(<b>1</b>)), [Cu-(5-Cl2HBz)-(bathophen)]-(NO₃)-1.5H₂O·CH₃OH (Cu-(<b>2</b>)), [Cu-(5-Cl2HBz)-(bipy)-(NO₃)-(H₂O)] (Cu-(<b>3</b>)), [Cu-(5-Cl2HBz)-(5,5'-bipy)-(NO₃)] (Cu-(<b>4</b>)), and [Cu-(5-Cl2HBz)-(<i>tert</i>-bipy)-(NO₃)]·2H₂O (Cu-(<b>5</b>)), where phen = 1,10-phenanthroline, bathophen = 4,7-diphenyl-1,10-phenanthroline, bipy = 2,2'-bipyridine, 5,5'-bipy = 5,5'-bipyridine, and <i>tert</i>-bipy = 4,4'-bis-(<i>tert</i>-butyl)-2,2'-bipyridine. Among the series, complex Cu-(<b>2</b>) 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-(<b>2</b>) 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.