New gold(I) organometallic compounds with biological activity in cancer cells

Benoît Bertrand, Andreia De Almeida, Evelien P.M. Van Der Burgt, Michel Picquet, Anna Citta, Alessandra Folda, Maria Pia Rigobello, Pierre Le Gendre, Ewen Bodio, Angela Casini

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

N-Heterocyclic carbene gold(I) complexes bearing a fluorescent coumarin ligand were synthesized and characterized by various techniques. The compounds were examined for their antiproliferative effects in normal and tumor cells in vitro; they demonstrated moderate activity and a certain degree of selectivity. The compounds were also shown to efficiently inhibit the selenoenzyme thioredoxin reductase (TrxR), whereas they were poorly effective towards the glutathione reductase (GR) and glutathione peroxidase enzymes. Notably, {3-[(7-methoxy-2-oxo-2H-chromen-4-yl)methyl]-1-methylimidazol-2-ylidene}(tetra-O-acetyl-1-thio-β-D-glucopyranosido)gold(I) (3) showed a pronounced inhibition of TrxR also in cell extracts, and it appeared to activate GR. Mechanistic information on the system derived from biotin-conjugated iodoacetamide assays showed selective metal binding to selenocysteine residues. Preliminary confocal fluorescence microscopy experiments proved that 3 enters tumor cells, where it reaches the nuclear compartment.

Original languageEnglish
Pages (from-to)4532-4536
Number of pages5
JournalEuropean Journal of Inorganic Chemistry
Volume2014
Issue number27
DOIs
StatePublished - 1 Sep 2014
Externally publishedYes

Keywords

  • Cancer
  • Carbenes
  • Coumarins
  • Enzymes
  • Gold

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