Synthesis, physico-chemical properties and biological analysis of newly obtained copper(II) complexes with pyrazole derivatives

• Published in: Journal of inorganic biochemistry 2014-06, Vol.135, p.68-76
• Main Authors: Grazul, Magdalena, Besic-Gyenge, Emina, Maake, Caroline, Ciolkowski, Michal, Czyz, Malgorzata, Sigel, Roland K.O., Budzisz, Elzbieta
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cancer cells; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - pharmacology; Copper - chemistry; Cytotoxic effect; DNA interactions; Drug Screening Assays, Antitumor; Drug Stability; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - physiology; Humans; Inhibitory Concentration 50; Metal(II) complexes; Pyrazole derivative; Pyrazoles - chemistry
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2014.02.014

Three new copper(II) complexes containing two different pyrazole bound ligands (1, 2) have been synthesized and characterized by IR, LSI-MS (liquid secondary ion mass spectrometry) and elemental analysis. 1H NMR spectra of the organic ligands have been recorded. We describe the influence of these complexes on particular cancer cell lines and DNA structure by MTT-assay [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide], APA (acid phosphatase activity)-assay or CD-spectroscopy and agarose gel electrophoresis methods, together with their physico-chemical properties such as lipophilicity and stability in aqueous solution. The cytotoxic effect on HUVEC (endothelial cells) for the most active complex 4 has been also investigated. Moreover, the ability of these complexes to induce apoptosis in cancer cells has been assessed by using fluorescence microscopy. Our results indicate that dichloridobis{1-[amino(thioxo)methyl]-5-hydroxy-3-phenyl-1H-pyrazole-κN2}copper(II) is the most potent complex among the tested complexes. [Display omitted] •New metal complexes with pyrazole derivatives were synthesized.•LogP values obtained for tested Cu(II) complexes indicate that they are lipophilic.•Complex 4 possesses higher cytotoxic activity than cisplatin.•Tested Cu(II) complexes might have the ability of cleaving DNA.•Complex 4 is capable of inducing apoptosis in cancer cells.