Nickel(II)-meclofenamate complexes: Structure, in vitro and in silico DNA- and albumin-binding studies, antioxidant and anticholinergic activity.

ABSTRACT

Five novel nickel(II) complexes with the non-steroidal anti-inflammatory drug sodium meclofenamate (Na-mclf) have been synthesized and characterized in the absence or co-existence of the nitrogen-donors imidazole (Himi), 2,2'-bipyridylamine (bipyam), 2,2'-bipyridylketoxime (Hpko) and 2,9-dimethyl-1,10-phenanthroline (neoc); namely [Ni(mclf-O)2(Himi)2(MeOH)2], [Ni(mclf-O)2(MeOH)4], [Ni(mclf-O)(mclf-O,O')(bipyam)(MeOH)]·0.25MeOH, [Ni(mclf-O,O')2(neoc)] and [Ni(mclf-O)2(Hpko-N,N')2]·MeOH·0.5H2O. The affinity of the complexes for calf-thymus (CT) DNA was investigated by various techniques and intercalation is suggested as the most possible interaction mode. The interaction of the complexes for bovine and human serum albumins was also investigated in order to determine the binding constants, concluding that the complexes bind reversibly to albumins for the transportation towards their target cells or tissues and their release upon arrival at biotargets. The antioxidant activity of the compounds was evaluated via their ability to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) free radicals and to reduce H2O2. For the determination of the anticholinergic ability of the complexes the in vitro inhibitory activity against the enzymes acetylcholinesterase and butyrylcholinesterase was evaluated and presented promising results. The in silico molecular modeling calculations employed provide useful insights for the understanding of the mechanism of action of the studied complexes at a molecular level. This applies on both the impairment of DNA by its binding with the studied complexes and transportation through serum albumins, as well as the ability of these compounds to act as anticholinergic agents.