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

Abstract

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 %.

• Authors: Julienne K Muenzner, Bernhard Biersack, Alexander Albrecht, Tobias Rehm, Ulrike Lacher, Wolfgang Milius, Angela Casini, Jing-Jing Zhang, Ingo Ott, Viktor Brabec, Olga Stuchlikova, Ion C Andronache, Leonard Kaps, Detlef Schuppan, Rainer Schobert
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 22 Issue 52 Pg. 18953-18962 (Dec 23 2016) ISSN: 1521-3765 [Electronic] Germany
• PMID: 27761940 (Publication Type: Journal Article)
• Copyright: © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Ferrous Compounds
• Metallocenes
• Reactive Oxygen Species
• Gold
• ferrocene

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology)
• Coordination Complexes (chemistry, pharmacology)
• Ferrous Compounds (chemistry)
• Gold (chemistry, pharmacology)
• Metallocenes (chemistry)
• Mice
• Reactive Oxygen Species (chemistry, metabolism)