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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 (CNN) (N, N'-nBu2 NHC) (CF3 SO3) (Pd1 d, HCNN=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.
Fong et al. (Mon,) studied this question.