In vitro cytotoxicity, DNA cleavage and SOD-mimic activity of copper(II) mixed-ligand quinolinonato complexes

Abstract

Six mixed-ligand copper(II) complexes with the composition [Cu(qui)(L)]BF4·xH2O (1–6), where Hqui=2-phenyl-3-hydroxy-4(1H)-quinolinone, L=2,2′-bipyridine (bpy) (1), 1,10-phenanthroline (phen) (2), bis(2-pyridyl)amine (ambpy) (3), 5-methyl-1,10-phenanthroline (mphen) (4), 5-nitro-1,10-phenanthroline (nphen) (5) and bathophenanthroline (bphen) (6), were prepared, fully characterized and studied for their in vitro cytotoxicity on human osteosarcoma (HOS) and human breast adenocarcinoma (MCF7) cancer cell lines. The overall promising results of the cytotoxicity were found for all the complexes, while the best results were achieved for complex 6, with IC50=2.6±0.8μM (HOS), and 1.3±0.5μM (MCF7). The interactions of the Cu(II) complexes 1–6 with calf thymus DNA were investigated by the UV–visible spectral titration. An agarose-gel electrophoretic method of oxidative damage determination to circular plasmid pUC19 was used to assess the ability of the complexes to act as chemical nucleases. A high effectiveness of DNA cleavage was observed for 2, 4 and 5. In vitro antioxidative activity of the complexes was studied by the superoxide dismutase-mimic (SOD-mimic) method. The best result was afforded by complex 1 with IC50=4.7±1.0μM, which corresponds to 10.2% of the native Cu,Zn-SOD enzyme activity. The ability of the tested complexes to interact with sulfur-containing biomolecules (cysteine and reduced glutathione) at physiological levels was proved by electrospray-ionization mass spectrometry (ESI-MS).