New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells. Issue 27 (13th May 2014)

• Record Type: Journal Article
• 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
• Other Names: Crans Debbie C. sponsoringEditor.; Nordlander Ebbe sponsoringEditor.
• Is Part Of: European journal of inorganic chemistry. Issue 27(2014)
• Page Start: 4532
• Page End: 4536
• Publication Date: 2014-05-13
• Subjects: Gold -- Carbenes -- Coumarins -- Enzymes -- Cancer; Chemistry, Inorganic -- Periodicals; Organometallic chemistry -- Periodicals; Bioinorganic chemistry -- Periodicals; Solid state chemistry -- Periodicals; 546
• DOI: 10.1002/ejic.201402248
• Languages: English
• ISSNs: 1434-1948

Abstract

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‐2 H ‐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 that3 enters tumor cells, where it reaches the nuclear compartment. Abstract : 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.