title: A new chromanone derivative isolated from Hypericum lissophloeus (Hypericaceae) potentiates GABAA receptor currents in a subunit specific fashion.
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.
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitätsplatz 4, A-8010 Graz, Austria. Electronic address: sara.crockett@uni-graz.at.
authors.forename: Sara
authors.initials: S
authors.lastname: Crockett
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstraße 28, CH-3012 Bern, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Baur
authors.affiliation: Institute of Pharmaceutical Chemistry, Department of Pharmaceutical Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
authors.forename: Olaf
authors.initials: O
authors.lastname: Kunert
authors.affiliation: Institute of Chemistry, Department of Inorganic Chemistry, University of Graz, Schubertstraße 1, A-8010 Graz, Austria.
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Belaj
authors.affiliation: Institute of Biochemistry and Molecular Medicine, University of Bern, Bühlstraße 28, CH-3012 Bern, Switzerland.
authors.forename: Erwin
authors.initials: E
authors.lastname: Sigel
mesh_terms: D000818:Animals; D002867:Chromones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D028084:Clusiaceae / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004305:Dose-Response Relationship, Drug; D008958:Models, Molecular; D015394:Molecular Structure; D009865:Oocytes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014981:Xenopus / Q000378:metabolism
chemical_list: D002867:Chromones; D011963:Receptors, GABA-A; D011994:Recombinant Proteins
keywords: Chromanone; GABA; GABA(A) receptor; Hypericaceae; Hypericum lissophloeus; Section Myriandra