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

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Abstract

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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Notes

  1. No signal corresponding to disproportionation or exchange phenomena was observed on HRMS spectrum.

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Acknowledgments

The “Centre National de la Recherche Scientifique” (ICMUB, UMR CNRS 6302) is gratefully thanked for financial support. Support was provided by the CNRS, the “Université de Bourgogne” and the “Conseil Régional de Bourgogne” through the 3MIM integrated project (“Marquage de Molécules par les Métaux pour l’Imagerie Médicale”) and PARI SSTIC n°6. Dr. Fanny Picquet, Marie-José Penouilh, and Marcel Soustelle are warmly acknowledged for technical support. E. B. is thankful for COST Action TD1004 financial support. A. C. thanks the University of Groningen for funding (Rosalind Franklin Fellowship). Authors are indebted to EU COST Actions CM1105 and CM1106 for stimulating discussion. M. P. R. acknowledges PRIN 20107Z8XBW granted by the Ministero dell’Istruzione, Università e Ricerca (MIUR) (Italy), CPDA130272 granted by the University of Padova (Italy), and Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (CIRCSMB).

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Authors and Affiliations

  1. Institut de Chimie Moléculaire, UMR 6302 CNRS Université de Bourgogne Franche Comté, 9 Avenue A. Savary, 21078, Dijon, France

    Benoît Bertrand, Michel Picquet, Pierre Le Gendre & Ewen Bodio

  2. Department of Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, Groningen, 9713 AV, The Netherlands

    Benoît Bertrand, Inge L. Franken & Angela Casini

  3. Department of Biomedical Sciences, University of Padova, via Ugo Bassi 58/b, Padua, Italy

    Anna Citta, Alessandra Folda & Maria Pia Rigobello

  4. Institute of Neuroscience, C.N.R., viale G. Colombo 3, Padua, Italy

    Valeria Scalcon

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  1. Benoît Bertrand
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  2. Anna Citta
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  3. Inge L. Franken
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  4. Michel Picquet
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  6. Valeria Scalcon
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  7. Maria Pia Rigobello
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  8. Pierre Le Gendre
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  9. Angela Casini
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  10. Ewen Bodio
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Correspondence to Angela Casini or Ewen Bodio.

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Bertrand, B., Citta, A., Franken, I.L. et al. Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis, characterization and evaluation as potential anticancer agents. J Biol Inorg Chem 20, 1005–1020 (2015). https://doi.org/10.1007/s00775-015-1283-1

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