Roberta Bertani

Synthesis of Cisplatin Analogues: Cytotoxic Efficacy and Anti-tumour Activity of Bis-Amidine and Bis-Iminoether Pt(II) Complexes

A series of new platinum(II) bis-amidine derivatives were prepared by addition of primary and secondary aliphatic amines to coordinated nitrile ligands in cis- and trans-[PtCl2(NCR)2] (R=Me, Ph, CH2Ph). The bis-amidine complexes were tested for their in vitro cytotoxicity on a panel of various human cancer cell lines. The results indicated that the trans isomers are more effective than the cis species, and in particular the benzamidine complex trans-[PtCl2{E-N(H)=C(NMe2) Ph}2] was the most active derivative and was able to circumvent acquired cisplatin resistance, thus suggesting a different mechanism of action compared to that exhibited by cisplatin. New benzyliminoether derivatives cis- and trans-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] were also prepared by addition of MeOH to cis- and trans-[PtCl2(NCCH2Ph)2] and the cytotoxic properties were evaluated in terms of cell growth inhibition against a panel of different types of human cancer cell lines. The complex cis-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] was significantly more potent than cisplatin against all tumour cell lines, including cisplatin-resistant ones. Moreover, the in vivo studies, performed on two transplantable tumour models, showed that cis-[PtCl2{E-N(H)=C(OMe)CH2Ph}2] exhibited a marked activity against murine L1210 leukaemia and Lewis lung carcinoma in terms of survival prolongation and tumour growth inhibition, respectively.