Organometallic Ruthenium Inhibitors of Glutathione-S-Transferase P1-1 as Anticancer Drugs

Details

Serval ID
serval:BIB_74D79F54C1DF
Type
Article: article from journal or magazin.
Collection
Publications
Title
Organometallic Ruthenium Inhibitors of Glutathione-S-Transferase P1-1 as Anticancer Drugs
Journal
Chemmedchem
Author(s)
Ang  W. H., De  L. A., Chapuis-Bernasconi  C., Juillerat-Jeanneret  L., Lo  B. M., Dyson  P. J.
ISSN
1860-7179 (Print)
Publication state
Published
Issued date
2007
Volume
2
Number
12
Pages
1799-1806
Notes
PT - JOURNAL ARTICLE
Abstract
Ruthenium-arene complexes conjugated to ethacrynic acid were prepared as part of a strategy to develop novel glutathione-S-transferase (GST) inhibitors with alternate modes of activity through the organometallic fragment, ultimately to provide targeted ruthenium-based anticancer drugs. Enzyme kinetics and electrospray mass spectrometry experiments using GST P1-1 and its cysteine-modified mutant forms revealed that the complexes are effective enzyme inhibitors, but they also rapidly inactivate the enzyme by covalent binding at Cys 47 and, to a lesser extent, Cys 101. They are highly effective against the GST Pi-positive A2780 and A2780cisR ovarian carcinoma cell lines, are among the most effective ruthenium complexes reported so far, and target ubiquitous GST Pi overexpressed in many cancers
Keywords
Carcinoma/Cell Line/Enzyme Inhibitors/Ethacrynic Acid/Kinetics/Ruthenium/Science/Switzerland
Pubmed
Web of science
Create date
29/01/2008 19:36
Last modification date
03/03/2018 18:22
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