Cytotoxic activity of new neodymium (III) complexes of bis-coumarins

Eur J Med Chem. 2004 Sep;39(9):765-75. doi: 10.1016/j.ejmech.2004.06.002.

Abstract

Complexes of neodymium (III) with bis-coumarins: 3,3'-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one); bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-2-yl-methane; bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-4-yl-methane; bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane were synthesized by reaction of neodymium (III) salt and the ligands, in amounts equal to metal:ligand molar ratio of 1:2. The complexes were prepared by adding an aqueous solution of neodymium (III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to ca. 5.0 by adding dilute solution of sodium hydroxide. The neodymium (III) complexes with bis-coumarins were characterized by different physicochemical methods-elemental analysis, IR-, (1)H- and (13)C-NMR-spectroscopies and mass-spectral data. The spectral data of neodymium (III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the Nd (III) complexes the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the nu(C=O) red shift observed, participation of the carbonyl groups in the coordination to the metal ion was also suggested. Cytotoxic screening by MTT assay was carried out. The complexes were tested on HL-60, HL-60/Dox and SKW-3 cell lines. The overall results from the preliminary screening program revealed that all of the new Nd (III) complexes reach 50% inhibition of the malignant cells proliferation and thus could be considered as biologically active. On the basis of the IC(50) values obtained compounds Nd(L(1))(OH).H(2)O and Nd(L(3))(OH).2H(2)O were found to exert superior activity in comparison to the remaining complexes.

MeSH terms

  • Adult
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Coumarins / chemical synthesis
  • Coumarins / chemistry
  • Coumarins / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • HL-60 Cells
  • Humans
  • Ligands
  • Molecular Structure
  • Neodymium / chemistry*
  • Organometallic Compounds / chemical synthesis
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*

Substances

  • Coumarins
  • Ligands
  • Organometallic Compounds
  • Neodymium