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

• DOI: 10.1002/cmdc.201800672
• Publication Date: 2018-11-16T19:23:50Z
• Authors: Maria Giulia Fabb...; Damiano Cirri; Alessandro Pratesi; Lorenzo Ciofi; Tiziano Marzo; Annalisa Guerri; Silvia Nistri; Alfonso Dell'Accio; Tania Gamberi; Mirko Severi; Andrea Bencini; Luigi Messori
• Keywords: Models, Molecular; Dose-Response Relationship, Drug; Molecular Structure; Cell Survival; Silver Compounds; Antineoplastic Agents; Crystallography, X-Ray; 01 natural sciences; 0104 chemical sciences; Structure-Activity Relationship; Organometallic Compounds; Tumor Cells, Cultured; Humans; anticancer drugs; fluorescence; mass spectrometry; silver carbene complexes; thioredoxin reductase; Drug Screening Assays, Antitumor; anticancer drugs; fluorescence; mass spectrometry; silver carbene complexes; thioredoxin reductase;; Methane; Cell Proliferation; Fluorescent Dyes

AbstractThe 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)2complexes.