Synthesis, X-ray structure, and anti-leukemic activity of oxovanadium(IV) complexes.

Abstract

In a systematic effort to identify and develop effective anticancer agents, four oxovanadium(IV) complexes with 1,10-phenanthroline (Phen) or 4,7-dimethyl-1,10-phenanthroline (Me2-Phen) as ligand(s) were synthesized and characterized. Among the four oxovanadium(IV) complexes synthesized, the crystal structure of the bis(phenanthroline)oxovanadium(IV) complex bis(1,10-phenanthroline)sulfatooxovanadium(IV) ([VO(SO4)(Phen)2], compound 1) has been determined. Compound 1 crystallized in the space group P2(1)/n with unit cell parameters a = 14.2125(17) A, b = 10.8628(13) A, c = 20.143(2) A, alpha = 90 degrees, beta = 102.569(2) degrees, gamma = 90 degrees, V = 3035.3(6) A3, and Z = 4. The refinement of compound 1 by full-matrix least-squares techniques gave an R factor of 0.0785 for 4356 independent reflections. The structure contains two enantiomorphous molecules, lambda and delta, which are related by an inversion center. Compound 1 exhibited 3.5-fold more potent cytotoxic activity against NALM-6 human leukemia cells than the mono(phenanthroline)oxovanadium(IV) complex (diaqua)(1,10-phenanthroline)sulfatooxovanadium(IV) ([VO(SO4)(Phen)(H2O)2], compound 2) (IC50 values: 0.97+/-0.10 microM versus 3.40+/-0.20 microM: P=0.0004). Methyl substitution in the phenanthroline ligand enhanced the anti-leukemic activity of the mono(phenanthroline)oxovanadium(IV) complex 4.4-fold (IC50 values: 0.78+/-0.10 microM, compound 4, versus 3.40+/-0.20 microM, compound 2; P=0.0003) and the anti-leukemic activity of the bis(phenanthroline)oxovanadium(IV) complex 5.7-fold (IC50 values: 0.17+/-0.02 microM, compound 3, versus 0.97+/-0.10 microM, compound 1; P=0.001). The leading oxovanadium compound, bis(4,7-dimethyl-1,10-phenanthroline)sulfatooxovanadium(IV) ([VO(SO4)(Me2-Phen)2], compound 3) triggered the production of reactive oxygen species (ROS) in human leukemia cells, caused G1-arrest and inhibited clonogenic growth at nanomolar concentrations.

• Authors: Y Dong, R K Narla, E Sudbeck, F M Uckun
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 78 Issue 4 Pg. 321-30 (Mar 2000) ISSN: 0162-0134 [Print] United States
• PMID: 10857913 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Ligands
• Reactive Oxygen Species
• oxovanadium IV
• Vanadates
• Methylcellulose

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Cycle (drug effects)
• Cell Division (drug effects)
• Cell Survival (drug effects)
• Crystallography, X-Ray
• Dose-Response Relationship, Drug
• Humans
• Inhibitory Concentration 50
• Ligands
• Methylcellulose (metabolism)
• Models, Chemical
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (drug therapy)
• Reactive Oxygen Species
• Time Factors
• Tumor Cells, Cultured
• Vanadates (chemistry, pharmacology)