title: Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid: Structure and biological features.
abstract: Copper(II) complexes with the non-steroidal anti-inflammatory drug tolfenamic acid (Htolf) with the oxygen-donor ligands methanol (MeOH) or N,N-dimethylformamide (DMF) and/or the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen) or pyridine (py) were synthesized and characterized. The crystal structures of five novel complexes were determined by X-ray crystallography where tolfenamic acid is deprotonated being in different binding modes. Equimolar quantities of CuCl2, tolf(-1) and bipy led to the formation of [Cu(tolf-O,O')(bipy)Cl] (1), while with a 1:2 Cu(II):tolf ratio, complexes [Cu(tolf-O,O')2(bipy)] (2), [Cu(tolf-O,O')2(bipyam)] · 0.5MeOH (3 0.5MeOH), [Cu(tolf-O,O')(tolf-O)(phen)(MeOH)] (4) and [Cu(tolf-O)2(py)2(MeOH)2] (5) were isolated. The interaction of the complexes with serum albumin proteins was studied by fluorescence spectroscopy with the determined binding constant bearing relative high values. The scavenging ability of the complexes towards 1,1-diphenyl-picrylhydrazyl, 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and hydroxyl radicals was investigated and the in vitro inhibitory activity against soybean lipoxygenase was evaluated and complexes 4 and 5 were the more active compounds among those tested. Spectroscopic (UV), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode and strength of the complexes to calf-thymus (CT) DNA suggesting intercalation as the most possible mode of binding. Competitive studies with ethidium bromide (EB) revealed the ability of the complexes to displace the DNA-bound EB. The biological properties of complexes 1-5 were evaluated in regard to previously reported complex [Cu2(tolf-O,O')4(DMF)2] (6).
authors.affiliation: Laboratory of Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Alketa
authors.initials: A
authors.lastname: Tarushi
authors.affiliation: Laboratory of Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Spyros
authors.initials: S
authors.lastname: Perontsis
authors.affiliation: Laboratory of Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Antonios G
authors.initials: AG
authors.lastname: Hatzidimitriou
authors.affiliation: Department of Nutrition and Dietetics, Faculty of Food Technology and Nutrition, Alexandrion Technological Educational Institution, Sindos, Thessaloniki, Greece.
authors.forename: Athanasios N
authors.initials: AN
authors.lastname: Papadopoulos
authors.affiliation: Laboratory of Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece.
authors.forename: Dimitris P
authors.initials: DP
authors.lastname: Kessissoglou
authors.affiliation: Laboratory of Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, GR-54124 Thessaloniki, Greece. Electronic address: gepsomas@chem.auth.gr.
authors.forename: George
authors.initials: G
authors.lastname: Psomas
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007364:Intercalating Agents / Q000138:chemical synthesis* / Q000737:chemistry; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D056831:Coordination Complexes; D016166:Free Radical Scavengers; D007364:Intercalating Agents; D062367:ortho-Aminobenzoates; D012710:Serum Albumin, Bovine; C009500:tolfenamic acid; D003300:Copper
keywords: Antioxidant activity; Copper(II) complexes; Interaction with CT DNA; Interaction with albumins; Tolfenamic acid