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New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells
Author(s) -
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
Publication year - 2014
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201402248
Subject(s) - cancer , group 2 organometallic chemistry , nanotechnology , chemistry , cancer research , biology , materials science , organic chemistry , genetics , molecule
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 that 3 enters tumor cells, where it reaches the nuclear compartment.