title: Cyclometalated Palladium(II) N-Heterocyclic Carbene Complexes: Anticancer Agents for Potent In Vitro Cytotoxicity and In Vivo Tumor Growth Suppression.
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'-nBu2 NHC)](CF3 SO3 ) (Pd1 d, HC^N^N=6-phenyl-2,2'-bipyridine, N,N'-nBu2 NHC=N,N'-di-n-butylimidazolylidene), displays potent killing activity toward cancer cell lines (IC50 =0.09-0.5 μm) but is less cytotoxic toward a normal human fibroblast cell line (CCD-19Lu, IC50 =11.8 μm). 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.
authors: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors: Tommy Tsz-Him
authors: TT
authors: Fong
authors: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors: Chun-Nam
authors: CN
authors: Lok
authors: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors: Clive Yik-Sham
authors: CY
authors: Chung
authors: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors: Yi-Man Eva
authors: YM
authors: Fung
authors: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors: Pui-Keong
authors: PK
authors: Chow
authors: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
authors: Pui-Ki
authors: PK
authors: Wan
authors: State Key Laboratory of Synthetic Chemistry, Institute of Molecular Functional Materials and Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China. cmche@hku.hk.|HKU Shenzhen Institute of Research and Innovation, Shenzhen, 518053, China. cmche@hku.hk.
authors: Chi-Ming
authors: CM
authors: Che
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008697:Methane / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D008819:Mice, Nude; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010165:Palladium / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; C030011:carbene; D010165:Palladium; D008697:Methane
keywords: N-heterocyclic carbenes; anticancer agents; palladium; proteomics; thiol reactivity