Preparation and characterization of novel trans-[PtCl2(amine) (isopropylamine)] compounds : Cytotoxic activity and apoptosis induction in ras-transformed cells

The synthesis and chemical characterization of three new transplatinum complexes of structural formula trans-[PtCl2(amine)(isopropylamine)] (amine = n,n-dimethylamine, propylamine, and butylamine), 1−3, are described. Cytotoxicity tests in tumor cell lines sensitive to cis-DDP (Jurkat, Hela, and Vero) and also in tumor cell lines overexpressing ras oncogenes and resistant to cis-DDP (HL-60 and Pam 212-ras) show that complexes 1 and 3 have higher cytotoxic activity than cisplatin. Moreover, these two trans-Pt(II) complexes kill Pam 212-ras cells through apoptosis induction. These results suggest that trans-PtCl2 complexes with asymmetric aliphatic amines may be considered a new class of biologically active trans-platinum drugs.