Design and synthesis of new camptothecin- Pt(II) dual drugs

The antitumor activity of cis-diaminedichloro-platinum (II) (DDP) was first reported by Rosenberg et al in 1969. The success of cisplatin paved the way for the second- and third-generation platinum(II) drugs, carboplatin and oxaliplatin, and presently platinum-based coordination complexes are among the most widely used antitumour agents in the clinic. Recently, many efforts have been made to overcome severe and sometimes life-threatening toxic side effects of Pt (II) complexes, low cellular uptake and relatively poor pharmacokinetic profiles, often correlated to the activation of drug resistance mechanisms by tumour cells. In this context we synthesised new Camptothecin-Pt complexes with different Pt-containing linkers ad we modelled their binding to the Topo I covalent complex with DNA.