Cytotoxicity of cis-platinum(II) cycloaliphatic amidine complexes: Ring size and solvent effects on the biological activity

A series of new platinum(II) amidine derivatives of the type cis-[PtCl2{Z-NHC(NHR)Me}2] (R = cyclopropyl, 1; cyclopentyl, 2; cyclohexyl, 3) were prepared in high yield by addition of the corresponding cyclic aliphatic amine RNH2 to the coordinated acetonitrile ligands in cis-[PtCl2(NCMe)2]. The solution behaviour of 1-3 has been studied in DMSO, PEG 400 (polyethylene glycol) and PEG-DME 500 (polyethylene glycol dimethylether). The amidine complexes 1-3 were evaluated for their cytotoxic properties against a panel of human tumor cell lines containing examples of cervix (HeLa), breast (MCF7), lung (A549) and colon (HCT-15) cancer. Moreover, the amidine complexes were tested for their cytotoxicity against normal human fibroblasts (HFF-1). For comparison purposes, the cytotoxicity of cisplatin was examined under the same experimental conditions. The results obtained showed that PEG and PEG-DME behave as good solvents to carry out biological assays with platinum complexes which are water-insoluble and unstable in DMSO. Complexes 2 and 3 exhibited a biological activity comparable to that of cisplatin.