In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands.

Details

Serval ID
serval:BIB_7E083338AFB7
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands.
Journal
Chemistry
Author(s)
Berger I., Hanif M., Nazarov A.A., Hartinger C.G., John R.O., Kuznetsov M.L., Groessl M., Schmitt F., Zava O., Biba F., Arion V.B., Galanski M., Jakupec M.A., Juillerat-Jeanneret L., Dyson P.J., Keppler B.K.
ISSN
0947-6539
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
14
Number
29
Pages
9046-57
Language
english
Notes
Publication types: Journal Article ;
Abstract
The synthesis and in vitro anticancer activity of dihalogenido(eta6-p-cymene)(3,5,6-bicyclophosphite-alpha-D-glucofuranoside)ruthenium(II) complexes are described. The compounds were characterized by NMR spectroscopy and ESI mass spectrometry, and the molecular structures of dichlorido-, dibromido- and diiodido(eta6-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. The complexes were shown to undergo aquation of the first halido ligand in aqueous solution, followed by hydrolysis of a P--O bond of the phosphite ligand, and finally formation of dinuclear species. The hydrolysis mechanism was confirmed by DFT calculations. The aquation of the complexes was markedly suppressed in 100 mM NaCl solution, and notably only very slow hydrolysis of the P--O bond was observed. The complexes showed affinity towards albumin and transferrin and monoadduct formation with 9-ethylguanine. In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside complex is the most cytotoxic compound in human cancer cell lines (IC50 values from 30 to 300 microM depending on the cell line).
Keywords
Antineoplastic Agents, Carbohydrate Metabolism, Carbohydrates, Cell Line, Cell Survival, Humans, Hydrolysis, Kinetics, Ligands, Magnetic Resonance Spectroscopy, Models, Molecular, Molecular Structure, Organic Chemistry Phenomena, Ruthenium Compounds
Pubmed
Web of science
Create date
03/10/2008 12:29
Last modification date
20/08/2019 15:39
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