Organometallic ruthenium inhibitors of glutathione-S-transferase P1-1 as anticancer drugs

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 ore effective enzyme inhibitors, but they also rapidly inactivate the enzyme by covalent binding at Cys 47 and, to a lesser extent, Cys 101. They ore highly effective against the GST Pi-positive A2780 and A2780cisR ovarian carcinoma cell lines, are among the most effective ruthenium complexes reported so for and target ubiquitous GST Pi overexpressed in many cancers.


Publié dans:
Chemmedchem, 2, 1799-1806
Année
2007
Publisher:
Wiley-Blackwell
ISSN:
1860-7179
Mots-clefs:
Laboratoires:




 Notice créée le 2012-07-04, modifiée le 2018-12-03


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