Design, Syntheses and Anticancer Activities of Platinum(IV) Prodrugs with Dihydrogen Phosphate as an Axial Ligand

CPL-1501 and CPL-1504, two platinum(IV) prodrugs with dihydrogen phosphate as one axial ligand, were synthesized from cisplatin and oxaliplatin, respectively, as the starting material, and characterized by elemental analysis, IR as well as C-13 and P-31 NMR. Their reduction potential was measured via the cyclic voltammetry. The standard MTT was used to evaluate anticancer activity of the two prodrugs against several human cancer cell lines. CPL-1501 has a good water-solubility (10 mg.mL(-1)) and water-stability. With the favorable E-p values, it can be readily reduced to an active prototype cisplatin in the oxygen-deprived micro-environment of cancer cells. The biological tests reveal that CPL-1501 is able to inhibit the growth of cancer cells and its anticancer activity is comparable to that of cisplatin but much greater than that of carboplatin, whereas CPL-1504 does not show significant activity, probably due to its lower E-p values.