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

Ternary metal-NSAID prodrugs: M(II)-diclofenac (M = Fe, Co, Zn) complexes of tris(2-pyridylmethyl)amine display “two-in-one activity” by exhibiting anti-proliferative and anti-inflammatory activities. [Display omitted] •Three M(II)-diclofenac complexes (M = Fe, Co and Zn) of a tripodal nitrogen liga...

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Published inInorganica Chimica Acta Vol. 486; pp. 663 - 668
Main Authors Lakshman, Triloke Ranjan, Deb, Jolly, Ghosh, Ivy, Sarkar, Subhash, Paine, Tapan Kanti
Format Journal Article
LanguageEnglish
Published Amsterdam Elsevier B.V 24.02.2019
Elsevier Science Ltd
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Summary:Ternary metal-NSAID prodrugs: M(II)-diclofenac (M = Fe, Co, Zn) complexes of tris(2-pyridylmethyl)amine display “two-in-one activity” by exhibiting anti-proliferative and anti-inflammatory activities. [Display omitted] •Three M(II)-diclofenac complexes (M = Fe, Co and Zn) of a tripodal nitrogen ligand were isolated.•The Zn(II) complex revealed a five-coordinate metal center with monodentate diclofenac.•All the complexes are stable in solution under cell culture conditions.•The complexes exhibit both anti-proliferative and anti-inflammatory activities. 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.
ISSN:0020-1693
1873-3255
DOI:10.1016/j.ica.2018.11.025