Erinacine E as a kappa opioid receptor agonist and its new analogs from a basidiomycete, Hericium ramosum

J Antibiot (Tokyo). 1998 Nov;51(11):983-90. doi: 10.7164/antibiotics.51.983.


A kappa opioid receptor binding inhibitor was isolated from the fermentation broth of a basidiomycete, Hericium ramosum CL24240 and identified as erinacine E (1). Three analogs of 1 were produced by fermentation in other media and by microbial biotransformation. Of these compounds, 1 was shown to be the most potent binding inhibitor. Preliminary SAR studies of these compounds indicated that all functional groups and side chains were required for the activity. Compound 1 was a highly-selective binding inhibitor for the kappa opioid receptor: 0.8 microM (IC50) for kappa, >200 microM for mu, and >200 microM for delta opioid receptor. Compound 1 suppressed electrically-stimulated twitch responses of rabbit vas deferens with an ED50 of 14 microM. The suppression was recovered by adding a selective kappa opioid receptor antagonist nor-binaltorphimine, indicating that 1 is a kappa opioid receptor agonist.

MeSH terms

  • Animals
  • Basidiomycota
  • Benzofurans / chemistry
  • Benzofurans / isolation & purification
  • Benzofurans / pharmacology*
  • Chromatography, High Pressure Liquid
  • Electric Stimulation
  • Fermentation
  • Guinea Pigs
  • Male
  • Rabbits
  • Receptors, Opioid, kappa / agonists*
  • Receptors, Opioid, kappa / metabolism
  • Spiro Compounds / chemistry
  • Spiro Compounds / isolation & purification
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship
  • Vas Deferens / drug effects
  • Vas Deferens / metabolism


  • Benzofurans
  • Receptors, Opioid, kappa
  • Spiro Compounds
  • erinacine E