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Title

Cyclometalated Palladium(II) N-Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression.

Authors

Fong, Tommy Tsz-Him; Lok, Chun-Nam; Chung, Clive Yik-Sham; Fung, Yi-Man Eva; Chow, Pui-Keong; Wan, Pui-Ki; Che, Chi-Ming

Abstract

Palladium(II) complexes are generally reactive toward substitution/reduction, and their biological applications are seldom explored. A new series of palladium(II) N-heterocyclic carbene (NHC) complexes that are stable in the presence of biological thiols are reported. A representative complex, [Pd(C^N^N)(N,N′-nBu2NHC)](CF3SO3) ( Pd1 d, HC^N^N=6-phenyl-2,2′-bipyridine, N,N′-nBu2NHC=N,N′-di-n-butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC50=0.09-0.5 μ m) but is less cytotoxic toward a normal human fibroblast cell line (CCD-19Lu, IC50=11.8 μ m). In vivo anticancer studies revealed that Pd1 d significantly inhibited tumor growth in a nude mice model. Proteomics data and in vitro biochemical assays reveal that Pd1 d exerts anticancer effects, including inhibition of an epidermal growth factor receptor pathway, induction of mitochondrial dysfunction, and antiangiogenic activity to endothelial cells.

Subjects

PALLADIUM; ANTINEOPLASTIC agents; TUMOR growth; CARBENES; FIBROBLASTS

Publication

Angewandte Chemie International Edition, 2016, Vol 55, Issue 39, p11935

ISSN

1433-7851

Publication type

Academic Journal

DOI

10.1002/anie.201602814

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