New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells

Authors

  • Benoît Bertrand,

    1. Department of Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands, http://www.rug.nl/research/medicinal-inorganic-chemistry/
    2. Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS Université de Bourgogne, UFR Sciences et Techniques 9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France
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    • These authors contributed equally to this work

  • Andreia de Almeida,

    1. Department of Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands, http://www.rug.nl/research/medicinal-inorganic-chemistry/
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    • These authors contributed equally to this work

  • Evelien P. M. van der Burgt,

    1. Department of Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands, http://www.rug.nl/research/medicinal-inorganic-chemistry/
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  • Michel Picquet,

    1. Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS Université de Bourgogne, UFR Sciences et Techniques 9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France
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  • Anna Citta,

    1. Department of Biomedical Sciences, University of Padua, Via Ugo Bassi 58/b, 35121 Padova, Italy
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  • Alessandra Folda,

    1. Department of Biomedical Sciences, University of Padua, Via Ugo Bassi 58/b, 35121 Padova, Italy
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  • Maria Pia Rigobello,

    1. Department of Biomedical Sciences, University of Padua, Via Ugo Bassi 58/b, 35121 Padova, Italy
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  • Pierre Le Gendre,

    1. Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS Université de Bourgogne, UFR Sciences et Techniques 9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France
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  • Ewen Bodio,

    Corresponding author
    1. Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS Université de Bourgogne, UFR Sciences et Techniques 9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France
    • Ewen Bodio, Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS Université de Bourgogne, UFR Sciences et Techniques 9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France

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

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  • Angela Casini

    Corresponding author
    1. Department of Pharmacokinetics, Toxicology and Targeting, Research Institute of Pharmacy, University of Groningen Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands, http://www.rug.nl/research/medicinal-inorganic-chemistry/
    • Ewen Bodio, Institut de Chimie Moléculaire de l'Université de Bourgogne, UMR 6302 CNRS Université de Bourgogne, UFR Sciences et Techniques 9 avenue Alain Savary, BP 47870, 21078 Dijon Cedex, France

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

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Abstract

N-Heterocyclic carbene gold(I) complexes bearing a fluorescent coumarin ligand were synthesized and characterized by various techniques. The compounds were examined for their antiproliferative effects in normal and tumor cells in vitro; they demonstrated moderate activity and a certain degree of selectivity. The compounds were also shown to efficiently inhibit the selenoenzyme thioredoxin reductase (TrxR), whereas they were poorly effective towards the glutathione reductase (GR) and glutathione peroxidase enzymes. Notably, {3-[(7-methoxy-2-oxo-2H-chromen-4-yl)methyl]-1-methylimidazol-2-ylidene}(tetra-O-acetyl-1-thio-β-D-glucopyranosido)gold(I) (3) showed a pronounced inhibition of TrxR also in cell extracts, and it appeared to activate GR. Mechanistic information on the system derived from biotin-conjugated iodoacetamide assays showed selective metal binding to selenocysteine residues. Preliminary confocal fluorescence microscopy experiments proved that 3 enters tumor cells, where it reaches the nuclear compartment.

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