Improving the anticancer activity of platinum(iv) prodrugs using a dual-targeting strategy with a dichloroacetate axial ligand.

Four novel platinum(iv) complexes, characteristic of DCA/TFA and with chloride ions as axial ligands, were designed and synthesized. This type of platinum(iv) complexes 1a-2b exhibited significant cytotoxic activity, and the cytotoxicity of 1b was the greatest among these four complexes, which was 20.61 fold and 7.65 fold higher than that of cisplatin against HepG-2 and NCI-H460 cancer cells, respectively. The result from the apoptosis assay of 1b was consistent with the result from the cytotoxicity assay. In addition, complexes 1a and 1b induced cell cycle arrest at the S phase on HepG-2 cells. Taken together, our data showed that Pt(iv) complex 1b released the corresponding Pt(ii) complex and DCA, and induced apoptosis as well as disruption of the mitochondrial membrane potential, establishing Pt(iv) complex 1b as a potential dual-targeting anticancer agent.