Ginkgolides and glycine receptors: a structure-activity relationship study

Stanislav Jaracz; Koji Nakanishi; Anders A. Jensen; Kristian Strømgaard

doi:10.1002/chem.200305473

Ginkgolides and glycine receptors: a structure-activity relationship study

Stanislav Jaracz, Koji Nakanishi, Anders A. Jensen, Kristian Strømgaard

40 Citations (Scopus)

Abstract

Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown that native ginkgolides are potent and selective antagonists of the inhibitory glycine receptor. Forty new ginkgolide derivatives have been prepared in good to high yields on milligram scales and investigated for their antagonistic properties at homomeric alpha 1 glycine receptors, thus providing the first structure-activity relationship study of ginkgolides at glycine receptors. A high-throughput screening assay showed that native ginkgolide C was the most potent ligand, and that manipulation of any of the hydroxyl groups led to loss of activity at alpha 1 glycine receptors.

Original language	English
Journal	Chemistry: A European Journal
Volume	10
Issue number	6
Pages (from-to)	1507-18
Number of pages	12
ISSN	0947-6539
DOIs	https://doi.org/10.1002/chem.200305473
Publication status	Published - 2004

Keywords

Diterpenes
Ginkgolides
Heterocyclic Compounds with 4 or More Rings
Lactones
Ligands
Molecular Conformation
Receptors, Glycine
Structure-Activity Relationship

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10.1002/chem.200305473

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title = "Ginkgolides and glycine receptors: a structure-activity relationship study",

abstract = "Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown that native ginkgolides are potent and selective antagonists of the inhibitory glycine receptor. Forty new ginkgolide derivatives have been prepared in good to high yields on milligram scales and investigated for their antagonistic properties at homomeric alpha 1 glycine receptors, thus providing the first structure-activity relationship study of ginkgolides at glycine receptors. A high-throughput screening assay showed that native ginkgolide C was the most potent ligand, and that manipulation of any of the hydroxyl groups led to loss of activity at alpha 1 glycine receptors.",

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year = "2004",

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language = "English",

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journal = "Chemistry: A European Journal",

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TY - JOUR

T1 - Ginkgolides and glycine receptors

T2 - a structure-activity relationship study

AU - Jaracz, Stanislav

AU - Nakanishi, Koji

AU - Jensen, Anders A.

AU - Strømgaard, Kristian

PY - 2004

Y1 - 2004

N2 - Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown that native ginkgolides are potent and selective antagonists of the inhibitory glycine receptor. Forty new ginkgolide derivatives have been prepared in good to high yields on milligram scales and investigated for their antagonistic properties at homomeric alpha 1 glycine receptors, thus providing the first structure-activity relationship study of ginkgolides at glycine receptors. A high-throughput screening assay showed that native ginkgolide C was the most potent ligand, and that manipulation of any of the hydroxyl groups led to loss of activity at alpha 1 glycine receptors.

AB - Ginkgolides from the Ginkgo biloba tree are diterpenes with a cage structure consisting of six five-membered rings and a unique tBu group. They exert a variety of biological properties. In addition to being antagonists of the platelet activating factor receptor (PAFR), it has recently been shown that native ginkgolides are potent and selective antagonists of the inhibitory glycine receptor. Forty new ginkgolide derivatives have been prepared in good to high yields on milligram scales and investigated for their antagonistic properties at homomeric alpha 1 glycine receptors, thus providing the first structure-activity relationship study of ginkgolides at glycine receptors. A high-throughput screening assay showed that native ginkgolide C was the most potent ligand, and that manipulation of any of the hydroxyl groups led to loss of activity at alpha 1 glycine receptors.

KW - Diterpenes

KW - Ginkgolides

KW - Heterocyclic Compounds with 4 or More Rings

KW - Lactones

KW - Ligands

KW - Molecular Conformation

KW - Receptors, Glycine

KW - Structure-Activity Relationship

U2 - 10.1002/chem.200305473

DO - 10.1002/chem.200305473

M3 - Journal article

C2 - 15034895

SN - 0947-6539

VL - 10

SP - 1507

EP - 1518

JO - Chemistry: A European Journal

JF - Chemistry: A European Journal

IS - 6

ER -

Ginkgolides and glycine receptors: a structure-activity relationship study

Abstract

Keywords

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