6533b86efe1ef96bd12cc939
RESEARCH PRODUCT
New Gold(I) Organometallic Compounds with Biological Activity in Cancer Cells
Anna CittaMichel PicquetBenoît BertrandBenoît BertrandAlessandra FoldaEvelien P. M. Van Der BurgtAndreia De AlmeidaPierre Le GendreEwen BodioMaria Pia RigobelloAngela Casinisubject
Thioredoxin reductaseGlutathione reductaseMECHANISMSInorganic Chemistrychemistry.chemical_compoundCoumarinsCHEMISTRYTARGETSN-HETEROCYCLIC CARBENESCancerchemistry.chemical_classificationSelenocysteineGlutathione peroxidaseGold; carbenes; coumarins; enzyme; CancerBiological activityLigand (biochemistry)EnzymesenzymechemistryBiochemistryCancer cellIodoacetamideCarbenesANTICANCER AGENTSCOMPLEXESGolddescription
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-beta-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 biotinconjugated 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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-09-01 |