Positive GABA(A) Receptor Modulators from Acorus calamus and Structural Analysis of (+)-Dioxosarcoguaiacol by 1D and 2D NMR and Molecular Modeling

Janine Zaugg, Eva Eickmeier, Samad Nejad Ebrahimi, Igor Baburin, Steffen Hering, Matthias Hamburger (Korresp. Autor*in)

    Veröffentlichungen: Beitrag in FachzeitschriftArtikelPeer Reviewed

    Abstract

    In a two-microelectrode voltage clamp with Xenopus laevis oocytes, a petroleum ether extract of Acorus calamus rhizomes enhanced the GABA-induced chloride current through GABA(A) receptors of the alpha(1)beta(2)gamma 2(S) subtype by 277% +/- 9.7% (100 mu g/mL). beta-Asarone (1), (+)-dioxosarcoguaiacol (2), (+)-shyobunone (3), and (+)-preisocalamenediol (4) were subsequently identified as main active principles through HPLC-based activity profiling and targeted isolation. The compounds induced maximum potentiation of the chloride current ranging from 588% +/- 126% (EC(50): 65.3 +/- 21.6 mu M) (2) to 1200% +/- 163% (EC(50): 171.5 +/- 34.6 mu M) (1), whereas (-)-isoshyobunone (5) and (-)-acorenone (6) exhibited weak GABAA modulating properties (5: 164% +/- 42.9%; EC(50): 109.4 +/- 46.6 mu M and 6: 241% +/- 23.1%; EC(50): 34.0 +/- 6.7 mu M). The relative configuration of 2 was established as 4R*8S*10R* by NOESY experiments and conformational analysis.
    OriginalspracheEnglisch
    Seiten (von - bis)1437-1443
    Seitenumfang7
    FachzeitschriftJournal of Natural Products
    Jahrgang74
    Ausgabenummer6
    DOIs
    PublikationsstatusVeröffentlicht - 2011

    ÖFOS 2012

    • 301206 Pharmakologie

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