Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis.

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State: Public
Version: Final published version
License: All rights reserved
Serval ID
serval:BIB_EFDF375073CE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis.
Journal
Inorganic chemistry
Author(s)
Ang W.H., Daldini E., Scolaro C., Scopelliti R., Juillerat-Jeannerat L., Dyson P.J.
ISSN
0020-1669 (Print)
ISSN-L
0020-1669
Publication state
Published
Issued date
30/10/2006
Peer-reviewed
Oui
Volume
45
Number
22
Pages
9006-9013
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
With a view to develop drugs that could resist hydrolysis in aqueous media, organometallic arene-capped ruthenium(II) 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (RAPTA) complexes bearing chelating carboxylate ligands have been prepared and studied. The new complexes, Ru(eta6-cymene)(PTA)(C2O4) (1) and Ru(eta6-cymene)(PTA)(C6H6O4) (2), were found to be highly soluble and kinetically more stable than their RAPTA precursor that contains two chloride ligands in place of the carboxylate ligands. They were also able to resist hydrolysis in water and exhibited significantly lower pKa values. Importantly, they showed a similar order of activity in inhibiting cancer cell-growth proliferation (as determined by in vitro assays) and exhibited oligonucleotide binding characteristics (as evidenced by matrix-assisted laser desorption ionization mass spectrometry) similar to those of the RAPTA precursor, hence realizing a strategy for developing a new generation of stable and highly water-soluble RAPTA adducts.
Keywords
Antineoplastic Agents/chemical synthesis, Antineoplastic Agents/chemistry, Antineoplastic Agents/pharmacokinetics, Antineoplastic Agents/pharmacology, Benzene Derivatives/chemical synthesis, Benzene Derivatives/chemistry, Benzene Derivatives/pharmacokinetics, Benzene Derivatives/pharmacology, Cell Line, Tumor, Drug Screening Assays, Antitumor, Drug Stability, Humans, Hydrolysis, Molecular Structure, Organometallic Compounds/chemical synthesis, Organometallic Compounds/chemistry, Organometallic Compounds/pharmacokinetics, Organometallic Compounds/pharmacology, Ruthenium/chemistry, Ruthenium/pharmacology
Pubmed
Web of science
Create date
30/01/2008 19:10
Last modification date
18/07/2020 6:19
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