Synthesis, Characterization, and in Vitro Studies of Bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]gold(I/III) Complexes

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• 作者：Wukun Liu ; Kerstin Bensdorf ; Maria Proetto ; Adelheid Hagenbach ; Ulrich Abram ; Ronald Gust
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：April 26, 2012
• 年：2012
• 卷：55
• 期：8
• 页码：3713-3724
• 全文大小：438K
• 年卷期：v.55,no.8(April 26, 2012)
• ISSN：1520-4804

文摘

Cationic bis[1,3-diethyl-4,5-diarylimidazol-2-ylidene]gold(I) complexes with 4-OCH₃ or 4-F substituents in the aromatic rings and Br^{鈥?/sup> (3a,b) or BF₄鈥?/sup> (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鈥?3鈥?4鈥?6鈥?tetra-O-acetyl-尾-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 IC₅₀ = 0.10 渭M (cisplatin, 1.6 渭M; 5-FU, 4.7 渭M). 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.}