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.

Ang, W.h., De Luca, A., Chapuis-Bernasconi, C., Juillerat-Jeanneret, L., Lo Bello, M., Dyson, P.j. (2007). Organometallic ruthenium inhibitors of glutathione-S-transferase P1-1 as anticancer drugs. CHEMMEDCHEM, 2(12), 1799-1806 [10.1002/cmdc.200700209].

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

De Luca A.
Membro del Collaboration Group
;
Lo Bello M.
Membro del Collaboration Group
;
2007-01-01

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 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.
2007
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10 - BIOCHIMICA
English
Antineoplastic Agents
Enzyme Inhibitors
Glutathione Transferase
Kinetics
Magnetic Resonance Spectroscopy
Organometallic Compounds
Ruthenium Compounds
Spectrometry, Mass, Electrospray Ionization
Ang, W.h., De Luca, A., Chapuis-Bernasconi, C., Juillerat-Jeanneret, L., Lo Bello, M., Dyson, P.j. (2007). Organometallic ruthenium inhibitors of glutathione-S-transferase P1-1 as anticancer drugs. CHEMMEDCHEM, 2(12), 1799-1806 [10.1002/cmdc.200700209].
Ang, Wh; De Luca, A; Chapuis-Bernasconi, C; Juillerat-Jeanneret, L; Lo Bello, M; Dyson, Pj
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/291831
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