Schmidt Claudia, Karge Bianka, Misgeld Rainer, Prokop Aram, Brönstrup Mark, Ott Ingo
Institute of Medicinal and Pharmaceutical Chemistry , Technische Universität Braunschweig , Beethovenstr. 55 , 38106 Braunschweig , Germany . Email:
Department of Chemical Biology , Helmholtz Centre for Infection Research and German Centre for Infection Research (DZIF) , Inhoffenstr. 7 , 38124 Braunschweig , Germany.
Medchemcomm. 2017 Jun 27;8(8):1681-1689. doi: 10.1039/c7md00269f. eCollection 2017 Aug 1.
A series of gold(i) complexes with two N-heterocyclic carbene ligands (biscarbene gold complexes) were prepared and evaluated for their effects against cancer cells and pathogenic bacteria. Proliferation inhibition was observed in cancer cells and in Gram-positive bacteria, whereas Gram-negative bacteria were less sensitive towards the compounds. The protein binding and cellular uptake were quantified and the combined results indicated a strong correlation between cellular bioavailability and antiproliferative effects. The biscarbene gold complexes inhibited bacterial and mammalian TrxRs with low to moderate potency. However, based on the obtained structure-activity-relationships and the high cellular accumulation levels, TrxR inhibition can be considered as a relevant contributor to the cellular pharmacology of biscarbene gold(i) complexes.
制备了一系列带有两个N-杂环卡宾配体的金（I）配合物（双卡宾金配合物），并评估了它们对癌细胞和病原菌的作用。在癌细胞和革兰氏阳性菌中观察到增殖抑制，而革兰氏阴性菌对这些化合物不太敏感。对蛋白质结合和细胞摄取进行了定量，综合结果表明细胞生物利用度与抗增殖作用之间存在强相关性。双卡宾金配合物以低至中等效力抑制细菌和哺乳动物的硫氧还蛋白还原酶（TrxRs）。然而，基于所获得的构效关系和高细胞积累水平，TrxR抑制可被视为双卡宾金（I）配合物细胞药理学的一个相关因素。
