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Ferrocenyl‐Coupled N‐Heterocyclic Carbene Complexes of Gold(I): A Successful Approach to Multinuclear Anticancer Drugs
Author(s) -
Muenzner Julienne K.,
Biersack Bernhard,
Albrecht Alexander,
Rehm Tobias,
Lacher Ulrike,
Milius Wolfgang,
Casini Angela,
Zhang JingJing,
Ott Ingo,
Brabec Viktor,
Stuchlikova Olga,
Andronache Ion C.,
Kaps Leonard,
Schuppan Detlef,
Schobert Rainer
Publication year - 2016
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201604246
Subject(s) - thioredoxin reductase , lipophilicity , carbene , chemistry , ferrocene , chorioallantoic membrane , stereochemistry , thioredoxin , biophysics , biochemistry , in vitro , biology , enzyme , electrode , electrochemistry , catalysis
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 IC 50 (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 %.