A new target for gold(I) compounds: Glutathione-S-transferase inhibition by auranofin

Anastasia De Luca, Christian G. Hartinger, Paul J. Dyson*, Mario Lo Bello, Angela Casini

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

25 Citations (Scopus)


Nowadays, gold compounds occupy a relevant position constituting a promising class of experimental anticancer metallodrugs. Several research efforts have been devoted to the investigations of the pharmacological properties of gold(I) complexes bearing phosphine ligands, such as the antiarthritic drug auranofin, that has also been shown to produce anticancer effects in vitro. In spite of the numerous studies that appeared in the literature the biological mechanisms of action of auranofin and analogues are still controversial. Here, we report on the inhibition effects of glutathione S-transferase P1-1 (GST P1-1) exerted by auranofin. The compound was able to inhibit GST P1-1 with a calculated IC50 of 32.9 +/- 0.5 mu M. Interestingly, the inhibition of GST P1-1 and its cysteine mutants by the gold(I) compound is essentially the same, suggesting that probably the cysteine residues are not so essential for enzyme inactivation in contrast to other reported inhibitors. High-resolution electrospray ionisation Fourier transform ion cyclotron mass spectrometry (ESI FT-ICR MS) studies allowed characterising the binding of the compound with GST enzymes at a molecular level, confirming that similar gold binding sites may be present in the wild-type protein and its Cys mutants. (C) 2012 Published by Elsevier Inc.

Original languageEnglish
Pages (from-to)38-42
Number of pages5
JournalJournal of Inorganic Biochemistry
Publication statusPublished - Feb-2013


  • Cytotoxicity
  • Gold complexes
  • GST enzymes
  • Mass spectrometry

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