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

• Published in: Journal of inorganic biochemistry 2011-09, Vol.105 (9), p.1187-1195
• Main Authors: Kovala-Demertzi, Dimitra, Staninska, Malgorzata, Garcia-Santos, Isabel, Castineiras, Alfonso, Demertzis, Mavroudis A.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic activity; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - metabolism; Antineoplastic Agents - pharmacology; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Cadmium - metabolism; Cell Line, Tumor; Chelating Agents - chemical synthesis; Chelating Agents - metabolism; Chelating Agents - pharmacology; Coordination Complexes - chemical synthesis; Coordination Complexes - metabolism; Coordination Complexes - pharmacology; Copper - metabolism; Crystal structures; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Female; Fibroblasts - cytology; Fibroblasts - drug effects; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - metabolism; Free Radical Scavengers - pharmacology; Free Radicals - antagonists & inhibitors; Free Radicals - metabolism; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Magnetic Resonance Spectroscopy; Manganese - metabolism; Meclofenamic acid; Meclofenamic Acid - analogs & derivatives; Meclofenamic Acid - chemical synthesis; Meclofenamic Acid - metabolism; Meclofenamic Acid - pharmacology; Metal complexes; Mice; Organ Specificity; Sod activity; Spectroscopic studies; Spectrum Analysis; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - pathology; Zinc - metabolism
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2011.05.025

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 2O) 2] ( 3), [Zn(meclo) 2(H 2O) 2] ( 4) and [Cd(meclo) 2(H 2O) 2] ( 5) were prepared and structurally characterized by means of vibrational, electronic and 1H and 13C 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 2O) 2] is a good superoxide scavenger. [Display omitted] New complexes of meclofenamic acid, HMeclo ( 1), with potentially interesting biological activities [Mn(meclo) 2] ( 2), [Cu(meclo) 2(H 2O) 2] ( 3), [Zn(meclo) 2(H 2O) 2] ( 4) and [Cd(meclo) 2(H 2O) 2] ( 5) were prepared and structurally characterized. Complex 5 exhibits the highest selectivity against MCF-7 and 4 shows the highest selectivity against T -24. [Cu(meclo) 2(H 2O) 2] was found to be good superoxide scavenger.