Discovery of novel (1S)-(-)-verbenone derivatives with anti-oxidant and anti-ischemic effects

Bioorg Med Chem Lett. 2013 Oct 1;23(19):5421-5. doi: 10.1016/j.bmcl.2013.07.038. Epub 2013 Jul 25.

Abstract

A series of novel (1S)-(-)-verbenone derivatives was synthesized bearing a 4-styryl scaffold. The synthesized compounds were tested for their anti-oxidant, anti-excitotoxic, and anti-ischemic activities. These derivatives significantly reduced oxygen-glucose deprivation-induced neuronal injury and N-methyl-D-aspartic acid-evoked excitotoxicity in cortical neurons. Furthermore, compound 3f was identified as a potent anti-ischemic agent in an in vitro ischemic model, potentially due to the inhibition of N-methyl-D-aspartic acid-evoked excitotoxicity and oxidative/nitrosative stress.

Keywords: Anti-excitotoxic activity; Anti-ischemic activity; Anti-oxidant activity; Cerebral ischemia; Verbenone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants* / chemical synthesis
  • Antioxidants* / chemistry
  • Antioxidants* / pharmacology
  • Bicyclic Monoterpenes
  • Cells, Cultured
  • Disease Models, Animal
  • Drug Discovery*
  • Ischemia / drug therapy
  • N-Methylaspartate / chemistry
  • Neurons / drug effects*
  • Neuroprotective Agents / chemical synthesis
  • Neuroprotective Agents / chemistry
  • Neuroprotective Agents / pharmacology
  • Oxidative Stress / drug effects
  • Terpenes / chemical synthesis
  • Terpenes / chemistry*
  • Terpenes / pharmacology

Substances

  • Antioxidants
  • Bicyclic Monoterpenes
  • Neuroprotective Agents
  • Terpenes
  • N-Methylaspartate
  • verbenone