Ferrocenyl‐Coupled N‐Heterocyclic Carbene Complexes of Gold(I): A Successful Approach to Multinuclear Anticancer Drugs. Issue 52 (17th November 2016)

• Record Type: Journal Article
• Authors: Muenzner, Julienne K.; Biersack, Bernhard; Albrecht, Alexander; Rehm, Tobias; Lacher, Ulrike; Milius, Wolfgang; Casini, Angela; Zhang, Jing‐Jing; Ott, Ingo; Brabec, Viktor; Stuchlikova, Olga; Andronache, Ion C.; Kaps, Leonard; Schuppan, Detlef; Schobert, Rainer
• Is Part Of: Chemistry. Volume 22:Issue 52(2016)
• Page Start: 18953
• Page End: 18962
• Publication Date: 2016-11-17
• Subjects: antitumor agents -- antivascular activity -- carbenes -- gold -- metal-based drugs; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201604246
• Languages: English
• ISSNs: 0947-6539

Abstract

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 complexes8 and10 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 complex10 was also tolerated well by mice where it led to a volume reduction of xenograft tumors by up to 80 %. Abstract : Iron to gold : The ferrocenyl substitution of gold(I) N‐heterocyclic carbene complexes augmented their interference with tumor cell redox homeostasis and their antivascular effects. The complex shown was well tolerated by mice and highly efficacious against invasive B16‐F10 melanoma xenograft tumors (see scheme; ROS=reactive oxygen species).