Synthesis, characterization, and biological activity of new mixed ammine/amine platinum(IV) complexes

A series of mixed ammine/amine platinum(IV) complexes with lipophilic ligands in their axial positions were designed, synthesized, and spectrally characterized. In vitro cytotoxicity evaluation of these complexes and their lead compounds have been carried out against A549, SMMC-7721, MCF-7, and SW480 human cancer cell lines. The introduction of carboxylate ions as leaving group can improve the aqueous solubility and stability of the platinum(II) complexes. The carboxylato ligands and chloride ligands in the axial position markedly increased the lipophilicity and cytotoxicity of compounds C4 and C5. Particularly, compound C5 showed two to eight times higher cytotoxicity than cisplatin and satraplatin against selected cell lines. For its oral activity and no cross-resistance potentiality, C5 is expected to be an antitumor platinum drug candidate. This novel class of platinum compounds represents a valuable lead in the development of new-generation agents capable of demonstrating cytotoxicity superior to that of the clinically established cisplatin.