Trans-platinum complexes with promising antitumor properties

Abstract

Wide range of dose-limiting toxicities and tumor resistance to drug are significant limitations of the successful use of cis-diamminedichloroplatinum (cisplatin). For a long time it was believed that generally trans-isomers of platinum containing complexes are devoid of biological activity. Data accumulated by the structure-activity relationship studies up to date, confirm that trans-platinum(II) and trans-platinum(IV) complexes often exhibit enhanced activity in cisplatin resistant cell lines in comparison to their cis-analogs, indicating that trans-platinum compounds follow some different pattern of antitumor activity in comparison to their cis-isomers. Trans-platinum complexes that have been tested to date and have shown to possess attractive antitumor properties represent diverse group of compounds, and can be classified according to the structure and the nature of nonleaving (amine) ligand as following: trans-ammine(amine) platinum(IV) complexes, trans-platinum(II) complexes with planar ligands, trans-platinum(II) complexes with heterocyclic amine ligands, trans-platinum(II) complexes with iminoether ligands, trans-platinum(II) complexes with asymmetric aliphatic amine ligands, bifunctional binuclear and trinuclear trans-platinum(II) complexes. Potential of trans-platinum complexes to follow some different mechanisms of cell killing in comparison to cis-DDP and thus circumvent cis-DDP resistance, raises interest for their further preclinical evaluation. © 2005 Bentham Science Publishers Ltd.