New Cisplatin Analogues—On the Way to Better Antitumor Agents

Abstract The clinical success of cisplatin ( cis ‐diamminedichloroplatinum( II )) in antitumor chemotherapy has encouraged an all‐out search for analogues with lower toxicity, improved therapeutic index and increased activity. Literally thousands of analogues, obtained by replacement of the ammine‐ and chloro‐ligands by other amines and anionic ligands, respectively, have been systematically screened for activity in experimental tumor models. Some of these analogues have been selected for clinical evaluation, but only very few of them appear to be promising antitumor agents. More recently, cisplatin analogues have been designed and synthesized on the basis of, inter alia, the following considerations: 1) platinum complexes with carrier molecules as ligands should prove useful for achieving increasing drug concentration in tumor tissues; 2) platinum complexes with chemotherapeutic agents as ligands could afford polyfunctional drugs with synergistic action; 3) complexes containing more than one platinum atom might be more effective than complexes containing only one platinum atom; 4) platinum complexes could be used as sensitizers in radiation therapy. In this paper, we shall give a brief account of the “traditional” analogues, and then critically discuss what we believe could be the new trends in the design of cisplatin analogues.