Synthesis, antiproliferative activity and DNA binding study of mixed ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates

Eur J Med Chem. 2011 Oct;46(10):5146-53. doi: 10.1016/j.ejmech.2011.08.029. Epub 2011 Aug 26.

Abstract

A novel series of ammine/cyclohexylamine platinum(II) complexes with 1-(substituted benzyl) azetidine-3, 3-dicarboxylates as leaving groups have been synthesized and characterized. All complexes were characterized by elemental analysis, IR, (1)H NMR, and ESI-MS spectra. The in vitro antiproliferative activities of the platinum-based compounds have been investigated against several human cancer cell lines, indicating that complexes 1 and 11 showed comparable cytotoxicity to those of cisplatin and oxaliplatin against four cell lines, superior to that of carboplatin. The results of drug safety evaluation (acute toxicity study) showed that complex 11 was much less toxic than cisplatin and oxaliplatin. Flow cytometry and agarose gel electrophoresis studies revealed that both complexes 1 and 11 induced apoptosis of tumor cells and demonstrated the binding affinity of complexes with pET22b plasmid DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Azetidinecarboxylic Acid / analogs & derivatives*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclohexylamines / chemical synthesis
  • Cyclohexylamines / chemistry*
  • Cyclohexylamines / pharmacology*
  • DNA / metabolism
  • Drug Screening Assays, Antitumor
  • Humans
  • Neoplasms / drug therapy
  • Organoplatinum Compounds / chemical synthesis
  • Organoplatinum Compounds / chemistry*
  • Organoplatinum Compounds / pharmacology*

Substances

  • Antineoplastic Agents
  • Cyclohexylamines
  • Organoplatinum Compounds
  • Azetidinecarboxylic Acid
  • DNA