Ang, Wee HanDe Luca, AnastasiaChapuis-Bernasconi, CatherineJuillerat-Jeanneret, LucienneLo Bello, MarioDyson, Paul J.2012-07-042012-07-042012-07-04200710.1002/cmdc.200700209https://infoscience.epfl.ch/handle/20.500.14299/83411WOS:000251678000016Ruthenium-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.Ethacrynic-AcidIn-VitroComplexesResistanceAdductstext::journal::journal article::research article