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A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis, Characterization, and Biological Studies
Author(s) -
Fabbrini Maria Giulia,
Cirri Damiano,
Pratesi Alessandro,
Ciofi Lorenzo,
Marzo Tiziano,
Guerri Annalisa,
Nistri Silvia,
Dell'Accio Alfonso,
Gamberi Tania,
Severi Mirko,
Bencini Andrea,
Messori Luigi
Publication year - 2019
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201800672
Subject(s) - thioredoxin reductase , carbene , chemistry , in vitro , internalization , fluorescence , stereochemistry , combinatorial chemistry , enzyme , biochemistry , thioredoxin , receptor , catalysis , physics , quantum mechanics
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.