Ferrocenyl-Coupled N-Heterocyclic Carbene Complexes of Gold(I): A Successful Approach to Multinuclear Anticancer Drugs

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• 作者：Dr. Julienne K. Muenzner ; Dr. Bernhard Biersack ; Alexander Albrecht ; Tobias Rehm ; Dr. Ulrike Lacher ; Dr. Wolfgang Milius ; Prof. Dr. Angela Casini ; Dr. Jing-Jing Zhang ; Prof. Dr. Ingo Ott ; Prof. Dr. Viktor Brabec ; Olga Stuchlikova ; Dr. Ion C. Andronache ; Leonard Kaps ; Prof. Dr. Dr. Detlef Schuppan and Prof. Dr. Rainer Schobert
• 刊名：Chemistry - A European Journal
• 出版年：2016
• 出版时间：December 23, 2016
• 年：2016
• 卷：22
• 期：52
• 页码：18953-18962
• 全文大小：3255K
• ISSN：1521-3765

文摘

Four gold(I) carbene complexes featuring 4-ferrocenyl-substituted imidazol-2-ylidene ligands were investigated for antiproliferative and antivascular properties. They were active against a panel of seven cancer cell lines, including multidrug-resistant ones, with low micromolar or nanomolar IC₅₀ (72 h) values, according to their lipophilicity and cellular uptake. The delocalized lipophilic cationic complexes 8 and 10 acted by increasing the reactive oxygen species in two ways: through a genuine ferrocene effect and by inhibiting the thioredoxin reductase. Both complexes gave rise to a reorganization of the F-actin cytoskeleton in endothelial and melanoma cells, associated with a G1 phase cell cycle arrest and a retarded cell migration. They proved antiangiogenic in tube formation assays with endothelial cells and vascular-disruptive on real blood vessels in the chorioallantoic membrane of chicken eggs. Biscarbene complex 10 was also tolerated well by mice where it led to a volume reduction of xenograft tumors by up to 80 %.