ABSTRACT
Six novel nickel(II) complexes with the non-steroidal anti-inflammatory drug mefenamic acid (Hmef) with the nitrogen-donor heterocyclic ligands 2,2'-bipyridine (bipy), 2,2'-bipyridylamine (bipyam), 1,10-phenanthroline (phen), 2,2'-dipyridylketone oxime (Hpko) or pyridine (py) and/or the oxygen-donor ligands CH3OH or H2O were synthesized and characterized by physicochemical and spectroscopic techniques. The crystal structures of [Ni(mef-O)2(bipy)(CH3OH)2] (1), [Ni(mef-O)2(phen)(CH3OH)2] (2), [Ni(mef-O,O')2(bipyam)] (3) and [Ni(mef-O)2(Hpko)2]âCH3OH (4·CH3OH) were determined by X-ray crystallography. The ability of the complexes to scavenge 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; complexes 3 and 4 were the most active compounds. Spectroscopic (UV and fluorescence), electrochemical (cyclic voltammetry) and physicochemical (viscosity measurements) techniques were employed in order to study the binding mode of the complexes to calf-thymus (CT) DNA and to calculate the corresponding binding constants; for all complexes, intercalation was the most possible mode of DNA-binding. The interaction of the complexes with serum albumins was studied by fluorescence emission spectroscopy and the values of the albumin-binding constants were determined.
Subject(s)
Mefenamic Acid/chemistry , Nickel/chemistry , Nickel/pharmacology , Nitrogen/chemistry , Animals , Cattle , Crystallography, X-Ray , DNA/chemistry , Electrochemical Techniques , Ligands , Molecular Structure , Spectrometry, Fluorescence , Spectrophotometry, Ultraviolet , Structure-Activity Relationship , ViscosityABSTRACT
The zinc(II) complex of the non-steroidal anti-inflammatory drug tolfenamic acid (=Htolf) in the presence of 2,2'-dipyridylketone oxime (=Hpko) as a N,N'-donor heterocyclic ligand, [Zn(tolf-O)2(Hpko-N,N')2]·MeOH (=1·MeOH), has been synthesized and characterized by physicochemical techniques including X-ray crystallography. The complex exhibits good binding affinity to human or bovine serum albumin with high binding constant values. Complex 1 and previously reported Zn-tolfenamato complexes were tested for their free radical scavenging activity and in vitro inhibitory activity against soybean lipoxygenase and exhibited significant activity with [Zn(tolf)2(1,10-phenantroline)] being the most active compound. The complexes interact with calf-thymus (CT) DNA via intercalation, and can displace the DNA-bound ethidium bromide with 1 exhibiting the highest binding constant to CT DNA.
Subject(s)
Albumins/drug effects , Antioxidants/pharmacology , DNA/drug effects , Zinc/chemistry , Animals , Antioxidants/chemistry , Cattle , Crystallography, X-Ray , Magnetic Resonance Spectroscopy , Spectrophotometry, UltravioletABSTRACT
The interaction of Zn(II) with the non-steroidal anti-inflammatory drug tolfenamic acid leads to the formation of the structurally characterized trinuclear [Zn(3)(tolfenamato)(6)(CH(3)OH)(2)] complex. In the presence of the N,N'-donor heterocyclic ligands 1,10-phenanthroline and 2,2'-bipyridine at a range of ratios, the mononuclear Zn complexes of the general formulae [Zn(tolfenamato)(N,N'-donor)Cl] and [Zn(tolfenamato)(2)(N,N'-donor)] have been isolated and structurally characterized by X-ray crystallography. The deprotonated tolfenamato ligands are coordinated to the Zn(II) ion through carboxylato oxygen atoms. Tolfenamic acid and its complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values.
