New cerium(III) complexes of coumarins - synthesis, characterization and cytotoxicity evaluation.

Complexes of cerium(III) with bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-2-yl-methane, bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-3-yl-methane and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-4-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 cerium(III) complexes with bis-coumarins were characterized by different physicochemical methods - elemental analysis, IR-, Raman-, (1)H NMR- and (13)C NMR-spectroscopy 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(CO) 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 three 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 bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-pyridin-2-yl-methane were evaluated on the SKW-3 cells. In order to elucidate some of the mechanistic aspects of the observed cytotoxic effects we evaluated the ability of this complex to trigger programmed cell death (apoptosis by means of agarose gel electrophoretic analysis of DNA, isolated from the cytosolic fraction of treated SKW-3 cells). In addition, microscopic morphological evaluation of the treated cells was carried out in order to establish morphological features indicative of programmed cell death.