Cationic nonsymmetric transplatinum complexes with piperidinopiperidine ligands. Preparation, characterization, in vitro cytotoxicity, in vivo toxicity, and anticancer efficacy studies

A series of complexes of the general formula trans-[PtCl ₂(Am)(pip-pip)]·HCl where pip-pip is 4-piperidinopiperidine and Am is NH₃, methylamine (MA), dimethylamine (DMA), n-propylamine (NPA), isopropylamine (IPA), n-butylamine (NBA), or cyclohexylamine (CHA) were prepared and characterized, and their cytotoxic properties against ovarian and colon cancer cells were evaluated. The trans-[PtCl₂(NH ₃)-(pip-pip)]·'HCl was significantly more potent than cisplatin in all the cisplatin-resistant ovarian cancer cell lines and was nearly as cytotoxic as cisplatin against colon cancer cells. In vivo studies in mice showed that the pip-pip complexes are significantly less toxic than cisplatin. Cisplatin was more efficacious than both trans-[PtCl ₂(NH₃)(pip-pip)]·HCl and trans-[PtCl ₂(NBA)(pip-pip)]·HCl in the A2780 and A2780cisR tumor xenograft models, consistent with its lower IC₅₀ values in A2780 cells but contrary to the higher IC₅₀ values in A2780cisR cells. In the colon cancer cell studies, trans-[PtCl₂(NH₃)(pip-pip)] ·HCl was slightly less potent than cisplatin in the in vitro studies but had efficacy comparable to that of cisplatin in the in vivo xenograft model.