Bioinorganic Chemistry and Applications 
Volume 2006 (2006), Article ID 25651, 9 pages
doi:10.1155/BCA/2006/25651

Synthesis, Characterization, and Cytotoxic Activity of New Lanthanum(III) Complexes of Bis-Coumarins

Irena Kostova,1 Georgi Momekov,2 Tzvetomira Tzanova,2 and Margarita Karaivanova2

 1Department of Chemistry, Faculty of Pharmacy, Medical University, 2 Dunav Street, Sofia 1000, Bulgaria
2Department of Pharmacology and Toxicology, Faculty of Pharmacy, Medical University, 2 Dunav Street, Sofia 1000, Bulgaria
Received 8 November 2004; Revised 16 March 2005; Accepted 21 March 2005

Abstract

Complexes of lanthanum(III) with bis-coumarins: 3,3′-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one) (H2L1) and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane (H2L2) were synthesized by reaction of lanthanum(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 lanthanum(III) salt to an aqueous solution of the ligand subsequently raising the pH of the mixture gradually to circa 5.0 by adding dilute solution of sodium hydroxide. The lanthanum(III) complexes with bis-coumarins were characterized by different physicochemical methods—elemental analysis, IR-, 1H-, and 13C-NMR-spectroscopies, and mass spectral data. The spectral data of lanthanum(III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the La(III) complexes, the ligands coordinated to the metal ion through both deprotonated hydroxyl groups. On the basis of the ν(C=O) red shift observed, participation of the carbonyl groups in the coordination with the metal ion was also suggested. In the present study, we performed a cytotoxic-effects screening of the lanthanum complexes with H2L1 and H2L2 in a panel of human tumor cell lines, using the standard MTT-dye reduction assay for cell viability. The panel consisted of the acute myeloid leukemia-derived HL-60 and the chronic myeloid leukemia-derived BV-173. Following a 24- hour treatment of BV-173 cells with lanthanum complex of H2L1 at 100 or 200 μM led to a DNA-laddering. The findings suggest that the observed cytotoxicity of the lanthanum complex of H2L1 on BV-173 is at least partly mediated through induction of programmed cell death.