Preparation, cytotoxicity and interactions with nucleophiles of three isomeric transplatinum complexes containing methylpiperidine ligands

Three isomeric complexes, trans-[PtCl₂(NH₃)(2- methylpiperidine)], trans-[PtCl₂(NH₃)(3-methylpiperidine)] and trans-[PtCl₂(NH₃)(4-methylpiperidine)], were prepared and their cytotoxicities against six ovarian cancer cell lines, three sensitive and three resistant to cisplatin, were measured. There were no significant differences in the cytotoxicities of the three isomers against these cell lines. The interactions of the three complexes with reduced glutathione (GSH) and with ubiquitin (Ub), as a model protein, were studied. The trans-[PtCl ₂(NH₃)(2-methylpiperidine)] reacted approximately twice as slowly with GSH as did the other two isomers. In the 1:1 interactions of the three complexes with ubiquitin (M_r = 8565 amu), trans-[PtCl ₂(NH₃)(3-methylpiperidine)] and trans-[PtCl ₂(NH₃)(4-methylpiperidine)] attained 100% modification while trans-[PtCl₂(NH₃)(2-methylpiperidine)] reached only less than 50% modification. Trans-[PtCl₂(NH₃)(2- methylpiperidine)] reacts significantly less efficiently with GSH and proteins than the other two isomers yet this is not reflected in the cytotoxicity values. These results indicate that for these complexes, in these cell lines, cytosolic detoxification probably does not play a dominant role in determining the cytotoxicity of the complexes.