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

Abstract 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 -[PtA 2 X 2 ] (where A 2 is either two monodentate or one bidentate amine ligand and X 2 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(NH 3 ) 2 (H 3 O) 2 ] (NO 3 ) 2 are highly toxic. Palladium(II) complexes, which are analogs of the active Platinum(II) compounds, have been found to be inactive.

[1]  R. Milburn,et al.  Oxygen Exchange in the Bis(oxalato)platinate(II) Ion and in Free Oxalate , 1965 .

[2]  R. Fraser,et al.  Infra-Red Dichroism and Protein Structure , 1952, Nature.

[3]  H. Gray,et al.  Mechanism of Substitution Reactions of Complex Ions. XVII.1 Rates of Reaction of Some Platinum(II) and Palladium(II) Complexes with Pyridine2 , 1960 .

[4]  G. Gale,et al.  Cis-dichlorodiammineplatinum (II). Persistent and selective inhibition of deoxyribonucleic acid synthesis in vivo. , 1970, Biochemical pharmacology.

[5]  B. Rosenberg,et al.  The successful regression of large solid sarcoma 180 tumors by platinum compounds. , 1970, Cancer research.

[6]  J. Glazer,et al.  Ionization of Bovine Serum Albumin Monolayers , 1952, Nature.

[7]  F. P. Dwyer,et al.  Effect of Inorganic Complex Ions on Transmission at a Neuromuscular Junction , 1957, Nature.

[8]  F. P. Dwyer,et al.  Biological Activity of Complex Ions , 1952, Nature.

[9]  D. Martin,et al.  Substitution Reactions of Trichloroammineplatinate(II) Ion and the trans Effect , 1964 .

[10]  R. Pearson,et al.  Mechanism of Substitution Reactions of Complex Ions. XII.1 Reactions of Some Platinum(II) Complexes with Various Reactants2 , 1957 .

[11]  H. C. Harder,et al.  Inhibitory effects of anti‐tumor platinum compounds on DNA, RNA and protein syntheses in mammalian cells in vitro , 1970, International journal of cancer.

[12]  E. Walker,et al.  Antitumor and antimitogenic properties of cis-dichloro(dipyridine)platinum(II). , 1971, Cancer research.

[13]  S. Ahrland,et al.  The relative affinities of ligand atoms for acceptor molecules and ions , 1958 .

[14]  R. Milburn,et al.  Oxalate Exchange in the Bisoxalatoplatinate(II) Ion , 1964 .

[15]  H. J. King.  251. Researches on ammines. Part IX. Diaquo-, hydroxoaquo-, and acidohydroxo-diammines of bivalent platinum , 1938 .

[16]  J. Trosko,et al.  Platinum Compounds: a New Class of Potent Antitumour Agents , 1969, Nature.

[17]  D. Martin,et al.  Trans-dichlorodiammineplatinum(II). Acid hydrolysis and the isotopic exchange of the chloride ligands , 1961 .