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

The silver(I) N‐heterocyclic carbene (NHC) complex bis(1‐(anthracen‐9‐ylmethyl)‐3‐ethylimidazol‐2‐ylidene) silver chloride ([Ag(EIA)2]Cl), bearing two anthracenyl fluorescent probes, has been synthesized and characterized. [Ag(EIA)2]Cl is stable in organic solvents and under physiological conditions, and shows potent cytotoxic effects in vitro toward human SH‐SY5Y neuroblastoma cells. The interactions of [Ag(EIA)2]Cl with a few model biological targets have been studied as well as its ability to be internalized in cells. The in vitro anticancer activity is apparently related to the level of drug internalization. Notably, [Ag(EIA)2]Cl does not react with a few model proteins, but is capable of binding the C‐terminal dodecapeptide of thioredoxin reductase hTrxR(488–499) and to strongly inhibit the activity of this enzyme. Binding occurs through an unconventional process leading to covalent binding of one or two carbene ligands to the C‐terminal dodecapeptide with concomitant release of the silver cation. To the best of our knowledge, this mode of interaction is reported here for the first time for Ag(NHC)2 complexes.

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

Section: Resultsmentioning

confidence: 99%

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

et al. 2018

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2015

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While N-heterocyclic carbenes (NHC) are ubiquitous ligands in catalysis for organic or industrial syntheses, their potential to form transition metal complexes for medicinal applications has still to be exploited. Within this frame, we synthesized new homo- and heterobimetallic complexes based on the Au(I)-NHC scaffold. The compounds were synthesized via a microwave-assisted method developed in our laboratories using Au(I)-NHC complexes carrying a pentafluorophenol ester moiety and another Au(I) phosphane complex or a bipyridine ligand bearing a pendant amine function. Thus, we developed two different methods to prepare homo- and heterobimetallic complexes (Au(I)/Au(I) or Au(I)/Cu(II), Au(I)/Ru(II), respectively). All the compounds were fully characterized by several spectroscopic techniques including far infrared, and were tested for their antiproliferative effects in a series of human cancer cells. They showed moderate anticancer properties. Their toxic effects were also studied ex vivo using the precision-cut tissue slices (PCTS) technique and initial results concerning their reactivity with the seleno-enzyme thioredoxin reductase were obtained.

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“…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.…”

Section: Fig 1 -Structures Of Organometallic Compounds Used For Medimentioning

confidence: 99%

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

et al. 2017

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

Cited by 124 publications

References 60 publications

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

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

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

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

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