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

J Inorg Biochem. 2009 Aug;103(8):1113-9. doi: 10.1016/j.jinorgbio.2009.05.009. Epub 2009 May 24.

Abstract

A series of new platinum(II) amidine derivatives of the type cis-[PtCl(2){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 RNH(2) to the coordinated acetonitrile ligands in cis-[PtCl(2)(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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amidines / chemistry*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity*
  • Cell Line, Tumor
  • Cisplatin / chemical synthesis*
  • Cisplatin / chemistry
  • Cisplatin / toxicity*
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Solutions
  • Solvents / chemistry*

Substances

  • Amidines
  • Antineoplastic Agents
  • Heterocyclic Compounds
  • Solutions
  • Solvents
  • Cisplatin