title: Synthesis, crystal structures and spectroscopy of meclofenamic acid and its metal complexes with manganese(II), copper(II), zinc(II) and cadmium(II). Antiproliferative and superoxide dismutase activity.
abstract: Some new complexes of meclofenamic acid (N-(2,6-dichloro-m-tolyl)anthranilic acid), Hmeclo (1), with potentially interesting biological activities are described. Complexes [Mn(meclo)(2)] (2), [Cu(meclo)(2)(H(2)O)(2)] (3), [Zn(meclo)(2)(H(2)O)(2)] (4) and [Cd(meclo)(2)(H(2)O)(2)] (5) were prepared and structurally characterized by means of vibrational, electronic and (1)H and (13)C NMR spectroscopies. The crystal structure of complexes [Cu(4)(meclo)(6)(OH)(2)(DMSO)(2)]2DMSO (3a) and [Cd(meclo)(2)(DMSO)(3)] (5a) have been determined by X-ray crystallography. Complex (3a) is a centrosymmetric tetramer built up around the planar cyclic Cu(2)(OH)(2) unit. Complex 5a is mononuclear seven-coordinated complex with the meclofenamato ligand behaving as a bidentate deprotonated chelating ligand. Intra and intermolecular hydrogen bonds stabilize these two structures, while the crystal packing is determined by π-π and C-H--π interactions. Meclofenamic acid and its metal complexes have been evaluated for antiproliferative activity in vitro against the cells of three human cancer cell lines, MCF-7 (breast cancer cell line), T24 (bladder cancer cell line), and A-549 (non-small cell lung carcinoma), and a mouse fibroblast L-929 cell line. Complex 5 exhibits the highest selectivity against MCF-7 and 4 shows the highest selectivity against T-24. Complexes 2-5 were found to be more potent cytotoxic agents against T-24 and complex 5 against MCF-7 cancer cell lines than the prevalent benchmark metallodrug, cis-platin. The superoxide dismutase activity was measured by the Fridovich test which showed that complex [Cu(meclo)(2)(H(2)O)(2)] is a good superoxide scavenger.
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: Malgorzata
authors: M
authors: Staninska
authors: Isabel
authors: I
authors: Garcia-Santos
authors: Alfonso
authors: A
authors: Castineiras
authors: Mavroudis A
authors: MA
authors: Demertzis
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002104:Cadmium / Q000378:metabolism; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D003300:Copper / Q000378:metabolism; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D005609:Free Radicals / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D008345:Manganese / Q000378:metabolism; D008469:Meclofenamic Acid / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D051379:Mice; D009928:Organ Specificity; D013057:Spectrum Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000473:pathology; D015032:Zinc / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002614:Chelating Agents; D056831:Coordination Complexes; D016166:Free Radical Scavengers; D005609:Free Radicals; D002104:Cadmium; D008345:Manganese; D008469:Meclofenamic Acid; D003300:Copper; D015032:Zinc