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

Abstract

Dichlorooxovanadium(IV) complexes of polypyridyl bases (B), viz., [VO(B)Cl₂] (<strong>1</strong> and <strong>2</strong>) of <em>N,N,N</em>-donor ligands 2-(2-pyridyl)-1,10-phenanthroline (pyphen in <strong>1</strong>) and 3-(pyridin-2-yl)dipyrido[3,2-a:2',3'-c]phenazine (pydppz in <strong>2</strong>) 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 <strong>1</strong> 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 <strong>1</strong> and <strong>2 </strong> are photocytotoxic towards HeLa (IC₅₀: 16.9 µM and 0.87 µM respectively) and MCF-7 (IC₅₀: 19.5 µM and 1.4 µM 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 <strong>1</strong> and <strong>2</strong> respectively. Complex <strong>2</strong> 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.