Structure–toxicity relationships for different types of dinuclear platinum complexes

Nine structurally distinct dinuclear platinum complexes have been evaluated in a novel model system for the investigation of renal epithelial toxicity of platinum drugs. The results showed that these compounds are toxic when applied at the basolateral side of renal epithelia, whereas their toxic effects on the apical side are negligible. Such a difference in toxicity of the complexes has been found to result from their poor uptake through the apical membrane, as compared to the basolateral membrane. Toxicity of the compounds on the basolateral side varies depending on their structure. Structure–toxicity relationships for the group of complexes with rigid ligands and for the group of complexes with flexible ligands are discussed. Among the dinuclear complexes with rigid ligands, sterically hindered complexes are less toxic, due to their poor uptake and low reactivity towards glutathione. Within the group of complexes with flexible ligands, cis-configured isomers are more toxic than their trans-counterparts.