TY - JOUR
T1 - Bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) as a novel apoptosis-inducing anticancer agent
AU - Narla, Rama Krishna
AU - Dong, Yanhong
AU - D'Cruz, Osmond J.
AU - Navara, Christopher
AU - Uckun, Fatih M.
PY - 2000/4
Y1 - 2000/4
N2 - 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.
AB - 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.
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M3 - Article
C2 - 10778988
AN - SCOPUS:0034005484
SN - 1078-0432
VL - 6
SP - 1546
EP - 1556
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -