title: 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.
authors: Dipartimento di Scienze Biomediche, Università di Padova, Viale G. Colombo 3, 35131 Padova, Italy.
authors: Anna
authors: A
authors: Citta
authors: Esther
authors: E
authors: Schuh
authors: Fabian
authors: F
authors: Mohr
authors: Alessandra
authors: A
authors: Folda
authors: Maria Lina
authors: ML
authors: Massimino
authors: Alberto
authors: A
authors: Bindoli
authors: Angela
authors: A
authors: Casini
authors: Maria Pia
authors: MP
authors: Rigobello
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival; D003600:Cytosol / Q000201:enzymology; D019281:Dimerization; D004354:Drug Screening Assays, Antitumor; D005980:Glutathione Reductase / Q000737:chemistry; D006046:Gold / Q000737:chemistry*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010084:Oxidation-Reduction; D061105:Peroxiredoxin III / Q000737:chemistry; D051381:Rats; D017382:Reactive Oxygen Species; D012834:Silver / Q000737:chemistry*; D013880:Thioredoxin-Disulfide Reductase / Q000737:chemistry / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; C030011:carbene; D012834:Silver; D006046:Gold; D061105:Peroxiredoxin III; D005980:Glutathione Reductase; D013880:Thioredoxin-Disulfide Reductase; D008697:Methane