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

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(H2O)2] (3), [Zn(meclo)2(H2O)2] (4) and [Cd(meclo)2(H2O)2] (5) were prepared and structurally characterized by means of vibrational, electronic and 1H and 13C NMR spectroscopies. The crystal structure of complexes [Cu4(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 Cu2(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(H2O)2] is a good superoxide scavenger.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideNew complexes of meclofenamic acid, HMeclo (1), with potentially interesting biological activities [Mn(meclo)2] (2), [Cu(meclo)2(H2O)2] (3), [Zn(meclo)2(H2O)2] (4) and [Cd(meclo)2(H2O)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(H2O)2] was found to be good superoxide scavenger.