0000000001309047
AUTHOR
Rainer Schobert
Ferrocenyl-Coupled N-Heterocyclic Carbene Complexes of Gold(I)
Four gold(I) carbene complexes featuring 4-ferro-cenyl-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 c…
Gold(I) Biscarbene Complexes Derived from Vascular-Disrupting Combretastatin A-4 Address Different Targets and Show Antimetastatic Potential
Gold N-heterocyclic carbene (NHC) complexes are an emerging class of anticancer drugs. We present a series of gold(I) biscarbene complexes with NHC ligands derived from the plant metabolite combretastatin A-4 (CA-4) that retain its vascular-disrupting effect, yet address different cellular and protein targets. Unlike CA-4, these complexes did not interfere with tubulin, but with the actin cytoskeleton of endothelial and cancer cells. For the highly metastatic 518A2 melanoma cell line this effect was accompanied by a marked accumulation of cells in the G1 phase of the cell cycle and a suppression of active prometastatic matrix metalloproteinase-2. Despite these mechanistic differences the co…
New 3-Aryl-2-(2-Thienyl)acrylonitriles with High Activity against Hepatoma Cells
New 2-(thien-2-yl)-acrylonitriles with putative kinase inhibitory activity were prepared and tested for their antineoplastic efficacy in hepatoma models. Four out of the 14 derivatives were shown to inhibit hepatoma cell proliferation at (sub-)micromolar concentrations with IC50 values below that of the clinically relevant multikinase inhibitor sorafenib, which served as a reference. Colony formation assays as well as primary in vivo examinations of hepatoma tumors grown on the chorioallantoic membrane of fertilized chicken eggs (CAM assay) confirmed the excellent antineoplastic efficacy of the new derivatives. Their mode of action included an induction of apoptotic capsase-3 activity, whil…
CCDC 1500972: Experimental Crystal Structure Determination
Related Article: 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|2016|Chem.-Eur.J.|22|18953|doi:10.1002/chem.201604246