title: Synthesis, characterization, and in vitro studies of bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]gold(I/III) complexes.
abstract: Cationic bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]gold(I) complexes with 4-OCH(3) or 4-F substituents in the aromatic rings and Br(-) (3a,b) or BF(4)(-) (7a,b) counterions were synthesized, characterized, and investigated for tumor growth inhibitory properties in vitro. Analogous to auranofin, the N-heterocyclic carbenes (NHCs) were also combined with a phosphine ligand (triphenylphosphine, 4a,b) and 2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl-1-thiolate (5a,b). The growth inhibitory effect against MCF-7, MDA-MB 231, and HT-29 cells, which is more than 10-fold higher than that of cisplatin or 5-FU, was independent of the oxidation state (Au(III), 6a,b) and the anionic counterion. Bis[1,3-diethyl-4,5-bis(4-fluorophenyl)imidazol-2-ylidene]gold(I) bromide 3b as the most cytotoxic compound reduced the growth of MCF-7 cells with IC(50) = 0.10 μM (cisplatin, 1.6 μM; 5-FU, 4.7 μM). The thioredoxin reductase (TrxR), the estrogen receptor (ER), and the cyclooxygenase (COX) enzymes, which have to be considered as possible targets based on the drug design, can be excluded from being involved in the mode of action.
authors.affiliation: Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Strasse 2 + 4, 14195 Berlin, Germany.
authors.forename: Wukun
authors.initials: W
authors.lastname: Liu
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bensdorf
authors.forename: Maria
authors.initials: M
authors.lastname: Proetto
authors.forename: Adelheid
authors.initials: A
authors.lastname: Hagenbach
authors.forename: Ulrich
authors.initials: U
authors.lastname: Abram
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001310:Auranofin / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D050607:Organogold Compounds / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013880:Thioredoxin-Disulfide Reductase / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D050607:Organogold Compounds; D001310:Auranofin; D013880:Thioredoxin-Disulfide Reductase; D005978:Glutathione