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

Complexes of cerium (III) with bis-coumarins: 3,3'-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one) and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane were synthesized by reaction of cerium (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 cerium (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 cerium (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 cerium (III) complexes were interpreted on the basis of comparison with the spectra of the free ligands. This analysis showed that in the Ce (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. In the present study we performed comparative evaluation of the cytotoxic effects of the two newly synthesized cerium complexes against the acute myeloid leukemia derived HL-60 and the chronic myeloid leukemia (CML)-derived BV-173. In addition the cytotoxic effects of Ce (III) complex with 3,3'-benzylidene-bis(4-hydroxy-2H-1-benzopyran-2-one) were evaluated on the CML-derived K-562 and LAMA-84 cells, characterized by relative low responsiveness to chemotherapy. The DNA isolated from the cytosolic fraction of BV-173 cells after 24 h treatment with the same complex (at 100 and 200 microM) demonstrated a laddering phenomenon that is indicative for apoptotic cell death.