Oxovanadium(IV) complexes of polypyridyl bases as photocytotoxic and DNA crosslinking agents

Chakravarty, Akhil R; Kumar, Arun ; Dixit, Akanksha ; Banerjee, Samya ; Mukherjee, Sanjoy ; Sahoo, Somarupa ; Karande, Anjali A.

Abstract

Dichlorooxovanadium(IV) complexes of polypyridyl bases (B), viz., [VO(B)Cl2] (1 and 2) of N,N,N-donor ligands 2-(2-pyridyl)-1,10-phenanthroline (pyphen in 1) and 3-(pyridin-2-yl)dipyrido[3,2-a:2',3'-c]phenazine (pydppz in 2) have been prepared, and their anticancer activity studied. The complexes show good solubility in most polar solvent and are
non-electrolytes. They show 1:1 electrolytic property in 20% aqueous DMF, and 1:2 electrolytic character in 20% aqueous DMF upon photo-irradiation with visible light (400–700 nm). Complex 1 shows DNA crosslinking property on dissociation of the V-Cl bond(s) as ascertained from its DNA melting profile and ethidium bromide displacement assay. The complexes 1 and 2 are photocytotoxic towards HeLa (IC50: 16.9 mM and 0.87 mM  respectively) and MCF-7 (IC50: 19.5 mM and 1.4 mM respectively) cancer cells, but exhibit less toxicity in normal embryonic fibroblast 3T3 cells with IC50 values of ~40 and ~25 µM in visible light (400-700 nm) for complexes 1 and 2 respectively. Complex 2 also displays light induced plasmid DNA cleavage activity. The light-induced cellular damage leads to generation of reactive oxygen species followed by apoptotic cell death.


Keyword(s)

Bioinorganic chemistry, Photocytotoxicity, Cytotoxicity, DNA crosslinks, DNA cleavage, Vanadium, Polypyridyl bases

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