Format

Send to

Choose Destination
See comment in PubMed Commons below
J Med Chem. 2011 Aug 11;54(15):5349-61. doi: 10.1021/jm200186n. Epub 2011 Jul 12.

Modulation of GABAA-receptors by honokiol and derivatives: subtype selectivity and structure-activity relationship.

Author information

  • 1Department of Pharmacology and Toxicology, University of Vienna, Vienna, Austria.

Abstract

A series of 31 analogues of the neolignan honokiol (a major constituent of Magnolia officinalis) was synthesized, and their effects on GABA(A) receptors expressed in Xenopus oocytes were investigated. Honokiol enhanced chloride currents (I(GABA)) through GABA(A) receptors of seven different subunit compositions with EC(50) values ranging from 23.4 μM (α(5)β(2)) to 59.6 μM (α(1)β(3)). Honokiol was most efficient on α(3)β(2) (maximal I(GABA) enhancement 2386%) > α(2)β(2) (1130%) > α(1)β(2) (1034%) > α(1)β(1) (260%)). On α(1)β(2)-receptors, N-substituted compounds were most active with 3-acetylamino-4'-O-methylhonokiol (31), enhancing I(GABA) by 2601% (EC(50) (α(1)β(2)) = 3.8 μM). Pharmacophore modeling gave a model with an overall classification accuracy of 91% showing three hydrophobic regions, one acceptor and one donor region. Unlike honokiol, 31 was most efficient on α(2)β(2)- (5204%) > α(3)β(2)- (3671%) > α(1)β(2)-receptors (2601%), suggesting a role of the acetamido group in subunit-dependent receptor modulation.

[PubMed - indexed for MEDLINE]

LinkOut - more resources

Full Text Sources

Chemical Information

Molecular Biology Databases

PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for American Chemical Society
    Loading ...
    Write to the Help Desk