Kappa-opioid receptor-selective dicarboxylic ester-derived salvinorin A ligands

Bioorg Med Chem Lett. 2013 May 15;23(10):2860-2. doi: 10.1016/j.bmcl.2013.03.111. Epub 2013 Apr 4.

Abstract

Salvinorin A, the active ingredient of the hallucinogenic plant Salvia divinorum is the most potent known naturally occurring hallucinogen and is a selective κ-opioid receptor agonist. To better understand the ligand-receptor interactions, a series of dicarboxylic ester-type of salvinorin A derivatives were synthesized and evaluated for their binding affinity at κ-, δ- and μ-opioid receptors. Most of the analogues show high affinity to the κ-opioid receptor. Methyl malonyl derivative 4 shows the highest binding affinity (Ki=2nM), analogues 5, 7, and 14 exhibit significant affinity for the κ-receptor (Ki=21, 36 and 39nM).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Camphanes
  • Diterpenes, Clerodane / chemistry
  • Diterpenes, Clerodane / isolation & purification
  • Diterpenes, Clerodane / pharmacology*
  • Dose-Response Relationship, Drug
  • Drugs, Chinese Herbal / chemistry
  • Drugs, Chinese Herbal / isolation & purification
  • Drugs, Chinese Herbal / pharmacology*
  • HEK293 Cells
  • Humans
  • Molecular Conformation
  • Panax notoginseng
  • Receptors, Opioid, kappa / agonists*
  • Salvia / chemistry
  • Salvia miltiorrhiza
  • Structure-Activity Relationship

Substances

  • Camphanes
  • Diterpenes, Clerodane
  • Drugs, Chinese Herbal
  • Receptors, Opioid, kappa
  • danshen dripping pill
  • salvinorin A