Structure–activity relationship studies for three new asymmetric cis-platinum(II) aminoethanol-based complexes

The design and synthesis of three asymmetrical platinum(II) analogues of cisplatin with substituents on the amine, varying in polarity and steric bulk is presented. Their biological activities, as studied using in vitro cytotoxicity studies in cisplatin sensitive and the corresponding cisplatin resistant cell lines, cellular uptake experiments and in a reaction with model DNA base GMP, are presented. All compounds exhibit promising cytotoxicity in the cisplatin sensitive cell lines albeit lower than cisplatin. On the other hand, the complexes partly overcome cisplatin resistance in the resistant cell lines. A direct correlation between cytotoxicity and cellular uptake was found. Conversely, the rate of reaction of all compounds with the model base GMP was found to be very similar and faster than cisplatin. It was therefore concluded that the difference in activity observed for these complexes is due to differential cellular uptake rather than the reactivity towards the cellular target of platinum complexes, nuclear DNA.

The design and synthesis of three new cis-platinum(II) aminoethanol-based complexes is presented. Subsequently the complexes are studied by in vitro cytotoxicity studies, cellular uptake experiments and in a reaction with model DNA base GMP. The results of these studies are used to improve our understanding of the activity of the complexes.Figure optionsDownload as PowerPoint slide