Studies on the antitumor activity of group VIII transition metal complexes. Part I. Platinum (II) complexes

A wide variety of Platinum(II) complexes have been investigated for antitumor activity against Sarcoma 180 in Swiss white female mice. In general, only neutral complexes exhibit activity while charged species are inactive and relatively nontoxic. A series of complexes of the type cis-[PtA2X2] (where A2 is either two monodentate or one bidentate amine ligand and X2 is either two monodentate or one bidentate anionic ligand) have been studied with A and X being systematically varied. This has resulted in the identification of at least ten potentially active antitumor drugs. Trans isomers are inactive in comparison with active cis complexes and the presence of cis-reactive ligands appears to be a necessary parameter for antitumor activity. Complexes with highly reactive ligands such as cis-[Pt(NH3)2(H3O)2] (NO3)2 are highly toxic. Palladium(II) complexes, which are analogs of the active Platinum(II) compounds, have been found to be inactive.