Cytotoxicity of the novel spin trapping compound 5-ethoxycarbonyl-3,5-dimethyl-pyrroline N-oxide (3,5-EDPO) and its derivatives

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5698-703. doi: 10.1016/j.bmcl.2007.07.054. Epub 2007 Aug 19.

Abstract

ESR spin trapping allows detection of superoxide radicals. Novel spin traps forming more stable superoxide adducts (t(1/2) ca. 12-55 min) were tested for their toxicity to cultured cells. The following toxicity ranking was obtained: 4,5-DPPO>4-BEMPO approximately 3-BEMPO>trans-3,5-EDPO>3,5-DPPO approximately 4,5-DiPPO approximately 4,5-EDPO>cis-3,5-EDPO approximately 3,5-DiPPO>DEPMPO. In conclusion, 4,5-EDPO, cis-3,5-EDPO and 3,5-DiPPO can be recommended for further investigation of superoxide in biological systems.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclic N-Oxides / chemical synthesis
  • Cyclic N-Oxides / chemistry*
  • Cyclic N-Oxides / toxicity*
  • Hepatocytes / drug effects
  • Hepatocytes / metabolism
  • Humans
  • Hydro-Lyases / metabolism
  • Isomerism
  • Molecular Structure
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Oxides / chemical synthesis
  • Oxides / chemistry*
  • Oxides / toxicity*
  • Rats
  • Spin Trapping*
  • Structure-Activity Relationship
  • Superoxides / metabolism

Substances

  • 5-ethoxycarbonyl-3,5-dimethyl-pyrroline N-oxide
  • Antineoplastic Agents
  • Cyclic N-Oxides
  • Oxides
  • Superoxides
  • Hydro-Lyases
  • lactate dehydratase