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.