Publication

Gold(I) Carbene Complexes Causing Thioredoxin 1 and Thioredoxin 2 Oxidation as Potential Anticancer Agents

Schuh, E., Pflueger, C., Citta, A., Folda, A., Rigobello, M. P., Bindoli, A., Casini, A. & Mohr, F., 14-Jun-2012, In : Journal of Medicinal Chemistry. 55, 11, p. 5518-5528 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Esther Schuh
  • Carolin Pflueger
  • Anna Citta
  • Alessandra Folda
  • Maria Pia Rigobello
  • Alberto Bindoli
  • Angela Casini
  • Fabian Mohr

Gold(I) complexes with 1,3-substituted imidazole-2-ylidene and benzimidazole-2-ylidene ligands of the type NHC-Au-L (NHC = N-heterocyclic carbene L = Cl or 2-mercapto-pyrimidine) have been synthesized and structurally characterized. The compounds were evaluated for their antiproliferative properties in human ovarian cancer cells sensitive and resistant to cisplatin (A2780S/R), as well in the nontumorigenic human embryonic kidney cell line (HEK-293T), showing in some cases important cytotoxic effects. Some of the complexes were comparatively tested as thioredoxin reductase (TrxR) and glutathione reductase (GR) inhibitors, directly against the purified proteins or in cell extracts. The compounds showed potent and selective TrxR inhibition properties in particular in cancer cell lines. Remarkably, the most effective TrxR inhibitors induced extensive oxidation of thioredoxins (Trxs), which was more relevant in the cancerous cells than in HEK-293T cells. Additional biochemical assays on glutathione systems and reactive oxygen species formation evidenced important differences with respect to the classical cytotoxic Au(I)-phosphine compound auranofin.

Original languageEnglish
Pages (from-to)5518-5528
Number of pages11
JournalJournal of Medicinal Chemistry
Volume55
Issue number11
Publication statusPublished - 14-Jun-2012

    Keywords

  • N-HETEROCYCLIC CARBENE, MITOCHONDRIAL PERMEABILITY TRANSITION, IN-VITRO CYTOTOXICITY, CELL-DEATH, THERAPEUTIC AGENTS, METAL-COMPLEXES, REDUCTASE, GLUTATHIONE, CANCER, LIGANDS

ID: 5590121