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

摘要

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 (Me-2-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) with unit cell parameters a = 14.2125(17) Angstrom, b = 10.8628(13) Angstrom, c = 20.143(2) Angstrom, alpha = 90 degrees, beta = 102.569(2)degrees, gamma = 90 degrees, V = 3035.3(6) Angstrom(3) 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 (di-aqua)( 1,10-phenanthroline)sulfatooxovanadium(IV) ([VO(SO4) (Phen) (H2O)(2)], compound 2) (IC50 values: 0.97 +/- 0.10 mu M versus 3.40 +/- 0.20 mu M; 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 mu M, compound 4, versus 3.40 +/- 0.20 mu M, 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 mu M, compound 3, versus 0.97 +/- 0.10 mu M, compound 1; P=0.001). The leading oxovanadium compound bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) ([VO(SO4)(Me-2-Phen)(2)], compound 3) triggered the production of reactive oxygen species (ROS) in human leukemia cells, caused G(1)-arrest and inhibited clonogenic growth at nanomolar concentrations. (C) 2000 Elsevier Science Inc. All rights reserved. [References: 38]