A Fluorescent Silver(I) Carbene Complex with Anticancer Properties: Synthesis,Characterization, and Biological Studies |
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| Authors: | Maria Giulia Fabbrini Damiano Cirri Dr Alessandro Pratesi Dr Lorenzo Ciofi Dr Tiziano Marzo Dr Annalisa Guerri Dr Silvia Nistri Alfonso Dell'Accio Tania Gamberi Dr Mirko Severi Prof Andrea Bencini Prof Luigi Messori |
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| Affiliation: | 1. Department of Chemistry “U. Schiff”, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy;2. Laboratory of Metals in Medicine (MetMed), Department of Chemistry “U. Schiff”, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy;3. Department of Pharmacy, University of Pisa, Via Bonanno Pisano 6, 56126 Pisa, Italy;4. Department of Experimental and Clinical Medicine, Largo Brambilla 3, 50134 Florence, Italy;5. Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Viale GB Morgagni 50, 50134 Florence, Italy |
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| Abstract: | 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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| Keywords: | anticancer drugs fluorescence mass spectrometry silver carbene complexes thioredoxin reductase |
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