A new chromanone derivative isolated from Hypericum lissophloeus (Hypericaceae) potentiates GABAA receptor currents in a subunit specific fashion

Bioorg Med Chem. 2016 Feb 15;24(4):681-5. doi: 10.1016/j.bmc.2015.12.037. Epub 2015 Dec 23.

Abstract

A phytochemical investigation of the lipophilic extract of Hypericum lissophloeus (smoothbark St. John's wort, Hypericaceae) was conducted, resulting in the isolation and identification of a new chromanone derivative: 5,7-dihydroxy-2,3-dimethyl-6-(3-methyl-but-2-enyl)-chroman-4-one (1). This compound was demonstrated to act as a potent stimulator of currents elicited by GABA in recombinant α1β2γ2 GABAA receptors, with a half-maximal potentiation observed at a concentration of about 4μM and a maximal potentiation of >4000%. Significant potentiation was already evident at a concentration as low as 0.1μM. Extent of potentiation strongly depends on the type of α subunit, the type of β subunit and the presence of the γ subunit.

Keywords: Chromanone; GABA; GABA(A) receptor; Hypericaceae; Hypericum lissophloeus; Section Myriandra.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromones / chemistry
  • Chromones / isolation & purification*
  • Chromones / pharmacology*
  • Clusiaceae / chemistry*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Models, Molecular
  • Molecular Structure
  • Oocytes / chemistry
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Receptors, GABA-A / metabolism*
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Xenopus / metabolism

Substances

  • Chromones
  • Receptors, GABA-A
  • Recombinant Proteins