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

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 sel...

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Bibliographic Details
Published in:European journal of inorganic chemistry 2014-09, Vol.2014 (27), p.4532-4536
Main Authors: Bertrand, Benoît, de Almeida, Andreia, van der Burgt, Evelien P. M., Picquet, Michel, Citta, Anna, Folda, Alessandra, Rigobello, Maria Pia, Le Gendre, Pierre, Bodio, Ewen, Casini, Angela
Format: Article
Language:English
Subjects:
Antiproliferatives
Cancer
Carbenes
Chemical Sciences
Confocal
Coumarins
Enzymes
Fluorescence
Glutathione
Gold
In vitro testing
Life Sciences
Microscopy
Reductases
Tumors
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Summary: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. Organometallic N‐heterocyclic carbene gold(I) complexes bearing a fluorescent coumarin ligand are synthesized, and their antiproliferative effects in normal and tumor cells in vitro are studied. Their biological properties may be due to inhibition of thioredoxin reductases. Fluorescence confocal microscopy allows the uptake of the compounds in cancer cells to be observed.
ISSN:1434-1948
1099-0682
DOI:10.1002/ejic.201402248