Biological evaluation of non-steroidal anti-inflammatory drugs-cobalt(II) complexes.
Cobalt(II) complexes with the non-steroidal anti-inflammatory drug mefenamic acid in the presence or absence of nitrogen donor heterocyclic ligands (2,2'-bipyridine, 1,10-phenanthroline or pyridine) have been synthesized and characterized with physicochemical and spectroscopic techniques. The experimental data suggest that mefenamic acid acts as deprotonated monodentate ligand coordinated to Co(II) ion through a carboxylato oxygen. The crystal structures of tetrakis(methanol)bis-(mefenamato)cobalt(II), 1 and (2,2'-bipyridine)bis(methanol)bis(mefenamato)cobalt(II), 2 have been determined by X-ray crystallography. The EPR spectra of complexes 1 and 2 in frozen solution reveal that they retain their structures. UV study of the interaction of the complexes with calf-thymus DNA (CT DNA) has shown that the complexes can bind to CT DNA and bis(methanol)bis(pyridine)bis-(mefenamato)cobalt(II) exhibits the highest binding constant. Competitive study with ethidium bromide (EB) has shown that the complexes can displace the DNA-bound EB indicating that they bind to DNA in strong competition with EB. The cyclic voltammograms of the complexes recorded in dmso solution and in the presence of CT DNA in 1 : 2 dmso : buffer (containing 150 mM NaCl and 15 mM trisodium citrate at pH 7.0) solution have shown that they can bind to CT DNA by the intercalative binding mode. Mefenamic acid and its cobalt(II) complexes exhibit good binding propensity to human or bovine serum albumin protein having relatively high binding constant values. The antioxidant activity of the compounds has been evaluated indicating their high scavenging activity against hydroxyl free radicals and superoxide radicals.
Dimiza
Filitsa
F
Department of General and Inorganic Chemistry, Faculty of Chemistry, Aristotle University of Thessaloniki, P.O. Box 135, GR-54124, Thessaloniki, Greece.
Papadopoulos
Athanasios N
AN
Tangoulis
Vassilis
V
Psycharis
Vassilis
V
Raptopoulou
Catherine P
CP
Kessissoglou
Dimitris P
DP
Psomas
George
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry* / Q000378:metabolism*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D001713:Biphenyl Compounds / Q000737:chemistry / Q000378:metabolism; D002417:Cattle; D003035:Cobalt / Q000737:chemistry*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004996:Ethidium / Q000737:chemistry / Q000378:metabolism; D005609:Free Radicals; D006801:Humans; D008528:Mefenamic Acid / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D010851:Picrates / Q000737:chemistry / Q000378:metabolism; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D001713:Biphenyl Compounds; D056831:Coordination Complexes; D005609:Free Radicals; D010851:Picrates; D012709:Serum Albumin; D008528:Mefenamic Acid; D003035:Cobalt; D004247:DNA; C004931:1,1-diphenyl-2-picrylhydrazyl; D004996:Ethidium