Antioxidant capacity and DNA-interaction studies of zinc complexes with a non-steroidal anti-inflammatory drug, mefenamic acid.

Abstract

Zinc(II) complexes of a non-steroidal anti-inflammatory drug, mefenamic acid(=Hmef) in the absence or presence of the nitrogen donor heterocyclic ligands 2,2'-bipyridine(=bipy), 2,2'-bipyridylamine(=bipyam), 2,2'-dipyridylketone oxime(=Hpko) or 1,10-phenanthroline(=phen) have been synthesized and characterized. The crystal structures of [Zn(mef-O,O')2(bipy)], 2, [Zn(mef-O)2(Hpko-N,N')2]·EtOH, 4 and [Zn(mef-O)(mef-O,O')(phen)(H2O)], 5, have been determined by X-ray crystallography showing distinct binding modes of mefenamato carboxylato group, bidentate in 2, monodentate in 4 or both in 5. Interaction studies of the complexes with calf-thymus DNA (CT DNA) have shown that complexes can bind to CT DNA with [Zn(mef-O)2(Hpko)2] exhibiting the highest binding constant to CT DNA (Kb = 1.93(±0.04) × 10(7) M(-1)). The complexes can bind to CT DNA via intercalation as concluded by DNA solution viscosity measurements. Competitive studies with ethidium bromide (EB) have shown that the complexes can displace the DNA-bound EB. The complexes exhibit good binding affinity to serum albumin proteins with [Zn(mef-O)2(H2O)4], 1 exhibiting the highest quenching ability (kq = 1.46 × 10(15) M(-1) s(-1) for human and 5.55 × 10(15) M(-1) s(-1) for bovine serum albumin). All compounds have been tested for their antioxidant and free radical scavenging activity as well as for their in vitro inhibitory activity against soybean lipoxygenase. The scavenging activity is low to moderate against 1,1-diphenyl-picrylhydrazyl (DPPH) radicals and high against hydroxyl and 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(+·)) radicals, with [Zn(mef-O)2(H2O)4], 1 (ABTS%, 0.1 mM: 94.75(±1.06)%; (·)OH%, 0.1mM: 96.69(±0.27)%; LOX: IC50 = 27.34(±0.90) μM) exhibiting the highest scavenging activity of the ABTS radical cation among the complexes. Additionally, the complexes exhibit higher scavenging and LOX inhibitory activity than free mefenamic acid (ABTS%, 0.1 mM: 66.32(±0.38)%; (·)OH%, 0.1 mM: 92.51(±0.44)%; LOX: IC50 = 48.52(±0.88) μM).