In a systematic effort to identify a potent
anticancer agent, we synthesized 15
oxovanadium(IV) complexes and examined their cytotoxic activity against 14 different human
cancer cell lines. The oxovanadium compounds included mono and bis ancillary
ligands of
1,10-phenanthroline (phen) [VO(phen), VO(phen)2, VO(Me2-phen), VO (Me2-phen)2, VO(Cl-phen), VO(Cl-phen)2, VO(NO2-phen), VO(NO2-phen)2], 2,2'-bipyridyl (bipy) [VO(bipy), VO(bipy)2, VO(Me2-bipy), VO(Me2-bipy)2], and 2-2'-bipyrimidine(bipym) [VO(bipym) and VO-(bipym)2], linked via
nitrogen atoms, and 5'-bromo-2'-hydroxyacetophenone (acph) [VO(acph)2], linked via
oxygen donor atom. The mono-chelated [VO(Me2-phen), compound 3] and bis-chelated-phen[VO(Me2-phen)2, compound 4] complexes were the most potent oxovanadium compounds and killed target
cancer cells at low micromolar concentrations. Notably, the dimethyl substitution of the
phenanthroline rings was essential for the anticancer activity of both compound 4 [VO(Me2-phen)2] and compound 3 [VO(Me2-phen)] because unsubstituted bis-chelated and mono-chelated phen
oxovanadium(IV) complexes [VO(phen), compound 1, or VO(phen)2, compound 2] were less active. Addition of a chloro or nitro group to the phen complexes did not significantly improve the cytotoxic activity of the unsubstituted
oxovanadium(IV) complexes. Irrespective of the
ligands, bis-chelated
phenanthroline containing compounds showed better activity than the mono-chelated
phenanthroline containing complexes. The marked differences in the cytotoxic activity of
oxovanadium(IV) complexes containing different heterocyclic ancillary
ligands suggest that the cytotoxic activity of these compounds is determined by the identity of the five-member bidentate
ligands, as well as the nature of the substitutents on the heterocyclic aromatic rings. Our results presented herein provide experimental evidence that oxovanadium compounds induce apoptosis in human
cancer cells. Oxovanadium compounds, especially the lead compound VO(Me2-phen)2, may be useful in the treatment of
cancer.