6533b7cffe1ef96bd1259b1e
RESEARCH PRODUCT
Ferrocenyl-Coupled N-Heterocyclic Carbene Complexes of Gold(I)
Angela CasiniAngela CasiniJulienne K. MuenznerUlrike LacherBernhard BiersackIon AndronacheIngo OttWolfgang MiliusDetlef SchuppanDetlef SchuppanRainer SchobertJing-jing ZhangTobias RehmOlga StuchlikovaOlga StuchlikovaLeonard KapsAlexander AlbrechtViktor BrabecViktor Brabecsubject
StereochemistryMetallocenesThioredoxin reductaseANTITUMOR-ACTIVITYDNA-BINDINGAntineoplastic AgentsCARCINOMA-CELLSCELLULAR UPTAKEPOTENTIAL ANTICANCER010402 general chemistrymetal-based drugs01 natural sciencesCatalysisantitumor agentschemistry.chemical_compoundMiceCoordination ComplexesAnimalsQDFerrous CompoundsIC50CANCER CELLSantivascular activitychemistry.chemical_classificationTube formationReactive oxygen species010405 organic chemistryChemistryOrganic ChemistryCell migrationGeneral ChemistryIN-VITROgold0104 chemical sciencescarbenesChorioallantoic membraneLipophilicityMETAL-COMPLEXESReactive Oxygen SpeciesTHIOREDOXIN REDUCTASE INHIBITORSCHORIOALLANTOIC MEMBRANE MODELCarbenedescription
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 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%.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-12-23 | Chemistry |