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...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2005-12, Vol.40 (12), p.1246-1254
Main Authors: Kostova, Irena, Manolov, Ilia, Momekov, Georgi, Tzanova, Tzvetomira, Konstantinov, Spiro, Karaivanova, Margarita
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Bis-coumarins
Carbon Isotopes
Cell Line, Tumor
Cell Survival - drug effects
Cerium (III) complexes
Cerium - chemistry
Coumarins - chemistry
Cytotoxic activity
DNA
DNA - drug effects
Drug Design
Drug Screening Assays, Antitumor
General aspects
Humans
IR- and NMR-spectra
Ligands
Magnetic Resonance Spectroscopy - methods
Magnetic Resonance Spectroscopy - standards
Medical sciences
Molecular Structure
Organometallic Compounds - chemical synthesis
Organometallic Compounds - chemistry
Organometallic Compounds - pharmacology
Pharmacology. Drug treatments
Protons
Reference Standards
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Summary: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 ν(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 μM) demonstrated a laddering phenomenon that is indicative for apoptotic cell death.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2005.07.010