Potent saccharinate-containing palladium(II) complexes for sensitization to cancer therapy

Palladium(II) (Pd^II) complexes are among the most promising anticancer compounds. Both 2`-benzoylpyridine thiosemicarbazone (BpT) and saccharinate (Sac) are efficient metal chelators with potent anticancer activity. To explore a more effective new anticancer drug, we synthesized a series of Sac and BpT-containing Pd^II complexes coordinated with thiosemicarbazone (TSC)-derived ligands, and characterized them through nuclear magnetic resonance (NMR), Fourier transformed infrared spectroscopy (FT-IR), elemental analysis, ultraviolet-visible spectroscopy (UV-Vis) and thermogravimetric analysis (TGA). Each target complex was composed of Pd^II, BpT, and one or two Sac molecules. Both the in vitro and in vivo anti-growth effects of those ligands and the obtained Pd^II complexes were investigated in the human lung adenocarcinoma cell lines A549 and Spc-A1. The coordination of Pd^II with the TSC-derivatives and Sac resulted in clearly greater anticancer activity than single ligands. These compounds were demonstrated to be safe for 293 T normal human kidney epithelial cells. The introduction of Sac into the TSC-derived Pd^II complex significantly enhanced anti-growth effects, and induced apoptosis of human lung cancer cells in vitro and in vivo in a dose dependent manner. Moreover, the Pd^II complex containing two Sac molecules showed the most promising therapeutic effects, thereby confirming that Sac increases the cancer therapeutic efficacy of Pd^II complexes and providing a new strategy for exploring anticancer drugs for potential clinical treatment.