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Med Chem Res (2013) 22:2395–2402 DOI 10.1007/s00044-012-0233-5

ORIGINAL RESEARCH

Copper(II) complexes with derivatives of pyrazole as potential antioxidant enzyme mimics Bogumiła Kupcewicz • Krzysztof Sobiesiak • Katarzyna Malinowska • Kamila Koprowska • Malgorzata Czyz • Bernhard Keppler • El_zbieta Budzisz

Received: 21 December 2011 / Accepted: 13 September 2012 / Published online: 26 September 2012  The Author(s) 2012. This article is published with open access at Springerlink.com

Abstract A series of six mononuclear Cu(II) complexes with pyrazole-based ligands: 5-(2-hydroxybenzoyl)-3-methyl1-(2-pyridinyl)-1H-pyrazol-4-phosphonic acid dimethyl ester (1a), 5-(2-hydroxyphenyl)-3-methyl-1-(2-pyridylo)-1H-pyrazole-4-carboxylic acid methyl ester (1b) and 1-benzothiazol -2-yl-5-(2-hydroxyphenyl)-3-methyl-1H-pyrazole-4-carboxylic acid methyl ester (1c) were characterized regarding to electrochemical and antioxidant properties. All complexes exhibit suitable Cu(II)/Cu(I) redox potential (E1/2) to act as antioxidant enzymes mimic. The five of these complexes were found to be trifunctional enzyme mimics possessing SOD, CAT and GPx-like catalytic activities. Moreover, Cu(II) complexes were capable to decrease ROS level in melanoma cells and observed effects were not merely a reflection of cytotoxicity. B. Kupcewicz (&)  K. Sobiesiak  E. Budzisz Department of Inorganic and Analytical Chemistry, Faculty of Pharmacy, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Curie-Sklodowskiej 9, 85-094 Bydgoszcz, Poland e-mail: [email protected] K. Malinowska Department of Chemistry and Clinical Biochemistry, Medical University of Lodz, Haller Square 1, 90-647 Lodz, Poland K. Koprowska  M. Czyz Department of Molecular Biology of Cancer, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland B. Keppler Institute of Inorganic Chemistry, University of Vienna, Wa¨hringerstr. 42, 1090 Vienna, Austria E. Budzisz Department of Cosmetic Raw Materials Chemistry, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151 Lodz, Poland

Keywords Enzyme mimic  Copper(II) complexes  Pyrazoles  Reactive oxygen species  Cyclic voltammetry

Introduction Reactive oxygen species (ROS) such as O2-, H2O2 and • OH are generated in cells through aerobic metabolic processes or as a result of interaction with exogenous agents. Low levels are essential for proper cell function, but excess levels of ROS are responsible for ‘oxidative stress’ which has been linked with the progression of ageing and many human diseases, e.g. neurogenerative, cardiovascular and cancer. Superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidase (GPx) are enzymes which act as a primary cellular defence system against oxidative damage in living organisms. Copper(II) has an important biological role in all living systems as an essential trace element (Linder and HazeghAzam, 1996). The Cu(II) complexes with organic ligands have been used as analgesic, antipyretic, antiinflammatory and a platelet anti-aggregating a