title: Anti-oxidant, in vitro, in vivo anti-inflammatory activity and antiproliferative activity of mefenamic acid and its metal complexes with manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II).
abstract: Some new complexes of mefenamic acid with potentially interesting biological activity are described. The complexes of mefenamic acid [Mn(mef)(2)(H(2)O)(2)], 1, [Co(mef)(2)(H(2)O)(2)], 2, [Ni(mef)(2)(H(2)O)(2)], 3, [Cu(mef)(2)(H(2)O)](2), 4 and [Zn(mef)(2)], 5, were prepared by the reaction of mefenamic acid, a potent anti-inflammatory drug with metal salts. Optical and infrared spectral data of these new complexes are reported. Monomeric six-coordinated species were isolated in the solid state for Mn(II), Ni(II) and Co(II), dimeric five-coordinated for Cu(II) and monomeric four-coordinated for Zn(II). In DMF or CHCl(3) solution the coordination number is retained and the coordinated molecules of water are replaced by solvent molecules. The anti-oxidant properties of the complexes were evaluated using the 1,1-diphenyl-2-picrylhydrazyl, DPPH, free radical scavenging assay. The scavenging activities of the complexes were measured and compared with those of the free drug and vitamin C. We have explored their ability to inhibit soybean lipoxygenase, beta-glucuronidase and trypsin- induced proteolysis. The complex [Mn(mef)(2)(H(2)O)(2)] exhibits the highest antioxidant activity and the highest inhibitory effect against the soybean lipogygenase (LOX), properties that are not demonstrated by mefenamic acid. Their inhibitory effects on rat paw edema induced by Carrageenan was studied and compared with those of mefenamic acid. The complex [Zn(mef)(2)] exhibited a strong inhibitory effect at 0.1 mmol/Kg B.W. (81.5 +/- 1.3% inhibition), superior to the inhibition induced by mefenamic acid at the same dose (61.5 +/- 2.3% inhibition). Mefenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines: MCF-7 (human breast cancer cell line), T24 (bladder cancer cell line), A-549 (non-small cell lung carcinoma) and a mouse fibroblast L-929 cell line. The copper(II) complex displays against T24, MCF-7 and L-929 cancer cell lines, IC(50) values in a microM range similar to that of the antitumor drug cis-platin and they are considered for further stages of screening in vitro and/or in vivo as agents with potential antitumor activity.
authors: Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, 45100, Ioannina, Greece. dkovala@cc.uoi.gr
authors: Dimitra
authors: D
authors: Kovala-Demertzi
authors: Dimitra
authors: D
authors: Hadjipavlou-Litina
authors: Malgorzata
authors: M
authors: Staninska
authors: Alexandra
authors: A
authors: Primikiri
authors: Chronis
authors: C
authors: Kotoglou
authors: Mavroudis A
authors: MA
authors: Demertzis
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002413:Cations, Divalent; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology; D003035:Cobalt / Q000737:chemistry; D056831:Coordination Complexes / Q000737:chemistry*; D003300:Copper / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D008345:Manganese / Q000737:chemistry; D008528:Mefenamic Acid / Q000737:chemistry*; D008670:Metals / Q000737:chemistry*; D051379:Mice; D009532:Nickel / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D015032:Zinc / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D002413:Cations, Divalent; D056831:Coordination Complexes; D008670:Metals; D009942:Organometallic Compounds; D008528:Mefenamic Acid; D003035:Cobalt; D008345:Manganese; D003300:Copper; D009532:Nickel; D015032:Zinc; D002945:Cisplatin