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

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.

A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis, Characterization, and Biological Studies

“… Structures of the ligand previously reported (left) and of the modified ligand 5 used in this work (right, see Scheme ).…”

Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis, characterization and evaluation as potential anticancer agents

“…In recent papers, NHC gold(I) compounds were shown to target both TrxR isoforms preferentially in tumour cell lines rather than in normal cells [41]. TrxR inhibition determines a shift to the oxidized forms of Trx and Prx III, allowing a large increase in reactive oxygen species (ROS) [42]. The second intracellular redox system is based on GSH, kept in a reduced state by glutathione reductase (GR), which is itself reduced by NADPH.…”

On the binding modes of metal NHC complexes with DNA secondary structures: implications for therapy and imaging

“…As an example, Ag(I) and Au(I) NHC complexes bearing a fluorescent anthracenyl ligand were examined for cytotoxicity in normal and tumor cells. 28 Fluorescence microscopy experiments showed that both compounds enter cells, and are particularly efficient in penetrating tumor cells where they reach the nuclear compartment.…”