Publication in Journal of Inorganic Biochemistry

Dinuclear copper(II) complexes with a bridging bis(chalcone) ligand reveal considerable in vitro cytotoxicity on human cancer cells and enhanced selectivity


Authors: Zdeněk Trávníček, Ján Vančo, Jan Belza, Giorgio Zoppellaro, Zdeněk Dvořák



A bis(chalcone) molecule (H2L) was synthesized via Aldol’s condensation from terephthalaldehyde and 2– hydroxyacetophenone and it was used as bridging ligand for the preparation of five dinuclear copper(II) complexes of the composition [Cu(N–N)(μ–L)Cu(N–N)](NO3)2⋅nH2O (= 0–2) (15), where N–N stands for a bidentate N-donor ligand such as phen (1,10-phenanthroline, 1), bpy (2,2-bipyridine, 2), mebpy (5,5-dimethyl- 2,2-dipyridine, 3), bphen (bathophenanthroline, 4) and nphen (5-nitro-1,10-phenanthroline, 5). The compounds were characterized by different suitable techniques to confirm their purity, composition, and structure. Moreover, the products were evaluated for their in vitro cytotoxicity on a panel of human cancer cell lines: ovarian (A2780), ovarian resistant to cisplatin (A2780R), prostate (PC3), osteosarcoma (HOS), breast (MCF7) and lung (A549), and normal fibroblasts (MRC-5), showing significant cytotoxicity in most cases, with IC50 ≈ 0.35–7.8 μM. Additionally, the time-dependent cytotoxicity and cellular uptake of copper, together with flow cytometric studies concerning cell-cycle arrest, induction of cell death and autophagy and induction of intracellular ROS/ superoxide production in A2780 cells, were also performed. The results of biological testing on A2780 cells pointed out a possible mechanism of action characterized by the G2/M cell cycle arrest and induction of apoptosis by triggering the intrinsic signalling pathway associated with the damage of mitochondrial structure and depletion of mitochondrial membrane potential.