Synthesis and characterization of new cis-[PtCl2(isopropylamine)(amine′)] compounds: cytotoxic activity and reactions with 5′-GMP compared with their trans-platinum isomers

The synthesis and characterization of four new cis-platinum compounds of structural formula cis-[PtCl2(NH2CH(CH3)2)(amine′)] (amine′=methylamine, dimethylamine, propylamine and butylamine) (2a–2d) are described. Cytotoxicity tests in tumor cell lines sensitive to cisplatin (CH1 and Pam 212) and resistant to cisplatin (CH1cisR, and Pam 212-ras) indicate that only compound 2a possesses cytotoxic activity in the cisplatin-sensitive cell line CH1, albeit much less than cis-DDP and also less than corresponding trans-platinum compounds with mixed aliphatic amines. The interactions of cis- (2a–2d) and trans- (3a–3d) [PtCl2(NH2CH(CH3)2)(amine′)] compounds with 5′-GMP in dilute NaClO4 (10 mM) were investigated by 1H NMR spectroscopy, and the progress of the reactions was followed overnight. In all cases two product peaks are observed in the cis-complexes, because the compounds are not symmetric. Temperature-dependent studies have been performed, but no significant variation in product structure is observed.