Fluorescent silver(I) and gold(I)-N-heterocyclic carbene complexes with cytotoxic properties: mechanistic insights

Metallomics. 2013 Aug;5(8):1006-15. doi: 10.1039/c3mt20260g.

Abstract

Silver(I) and gold(I)-N-heterocyclic carbene (NHC) complexes bearing a fluorescent anthracenyl ligand were examined for cytotoxicity in normal and tumor cells. The silver(I) complex exhibits greater cytotoxicity in tumor cells compared with normal cells. Notably, in cell extracts, this complex determines a more pronounced inhibition of thioredoxin reductase (TrxR), but it is ineffective towards glutathione reductase (GR). Both gold and silver complexes lead to oxidation of the thioredoxin system, the silver(I) derivative being particularly effective. In addition, the dimerization of peroxiredoxin 3 (Prx3) was also observed, demonstrating the ability of these compounds to reach the mitochondrial target. The fluorescence microscopy visualization of the subcellular distribution of the complexes shows a larger diffusion of these molecules in tumor cells with respect to normal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival
  • Cytosol / enzymology
  • Dimerization
  • Drug Screening Assays, Antitumor
  • Glutathione Reductase / chemistry
  • Gold / chemistry*
  • Humans
  • Liver / enzymology
  • Methane / analogs & derivatives*
  • Methane / chemistry
  • Microscopy, Fluorescence
  • Mitochondria / enzymology
  • Mitochondria / metabolism
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Oxidation-Reduction
  • Peroxiredoxin III / chemistry
  • Rats
  • Reactive Oxygen Species
  • Silver / chemistry*
  • Thioredoxin-Disulfide Reductase / chemistry
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Reactive Oxygen Species
  • carbene
  • Silver
  • Gold
  • Peroxiredoxin III
  • Glutathione Reductase
  • Thioredoxin-Disulfide Reductase
  • Methane