Combining anti-inflammatory and anti-proliferative activities in ternary metal-NSAID complexes of a polypyridylamine ligand

Abstract

To develop metallodrugs exhibiting anti-proliferative and anti-inflammatory activities, anti-proliferative supporting ligand and co-ligand NSAID were combined in ternary metal complexes. Three ternary complexes with the general formula [(TPA)MII(diclofenac)]+ (TPA = tris(2-pyridylmethyl)amine, M = iron, cobalt and zinc) have been isolated and characterized. The crystal structure of the zinc(II)-diclofenac complex reveals a five-coordinate metal center, in which diclofenac coordinates in monodentate mode through one carboxylate oxygen. The iron(II) and zinc(II) complexes exhibit anti-proliferative effect on MDA-MB-231 human breast cancer cells with the IC50 value of 9.45 μM and 9.00 μM, respectively. On the contrary, the cobalt(II) complex shows less cytotoxicity due to its tendency toward oxidative degradation under aerobic conditions. The complexes display anti-inflammatory activity through inhibition of COX-pathways.