期刊
JOURNAL OF INORGANIC BIOCHEMISTRY
卷 116, 期 -, 页码 163-171出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jinorgbio.2012.07.009
关键词
Copper(II) complexes; Quinolinone derivatives; In vitro cytotoxicity; DNA interactions; DNA cleavage; SOD-mimic activity
资金
- Ministry of Education, Youth and Sports of the Czech Republic [MSM6198959218]
- Operational Program Research and Development for Innovations - European Social Fund [CZ.1.05/2.1.00/03.0058]
- Operational Program Education for Competitiveness - European Social Fund of the Ministry of Education, Youth and Sports of the Czech Republic [CZ.1.07/2.3.00/20.0017]
- Palacky University [PrF_2011_014, PrF_2012_009]
- Grant Agency of the Czech Republic [P207/11/0841]
Six mixed-ligand copper(II) complexes with the composition [Cu(qui)(L)]BF4 center dot xH(2)O (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 +/- 0.8 mu M (HOS), and 1.3 +/- 0.5 mu M (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 +/- 1.0 mu M, 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). (c) 2012 Elsevier Inc. All rights reserved.
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