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

High Resolution Image Download MS PowerPoint Slide 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)(NO 3 )] (Cu( 1 )), [Cu(5-Cl2HBz)(bathophen)](NO 3 )1.5H 2 O·CH 3 OH (Cu( 2 )), [Cu(5-Cl2HBz)(bipy)(NO 3 )(H 2 O)] (Cu( 3 )), [Cu(5-Cl2HBz)(5,5′-bipy)(NO 3 )] (Cu( 4 )), and [Cu(5-Cl2HBz)( tert -bipy)(NO 3 )]·2H 2 O (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 (IC 50 = 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.