Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 50, Issue 7, Pages 1610-1617Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm070003n
Keywords
-
Categories
Funding
- NIGMS NIH HHS [GM MH068817] Funding Source: Medline
Ask authors/readers for more resources
Ginkgolides are antagonists of the inhibitory ligand-gated ion channels for the neurotransmitters glycine and gamma-aminobutyric acid (GABA). In this study the ginkgolide structure was modified in order to investigate the minimum structural requirements for glycine receptor antagonism. The five native ginkgolides and a series of 29 ginkgolide derivatives were characterized at the three glycine receptor subtypes alpha 1, alpha 1 beta, and alpha 2, which revealed that only minor changes in the ginkgolide skeleton were allowed for maintaining glycine receptor antagonism. A pharmacophore model was generated and applied in a virtual screening of a compound database (300 000 compounds), resulting in the identification of 31 hits. Twenty-seven of these hits were screened for biological activity, but none displayed antagonist activity at the glycine receptors. This strongly suggests the importance of other pharmacophore components in the binding of ginkgolides to glycine receptors, and we propose that the structural rigidity of the ginkgolide molecule may be crucial for its glycine receptor activity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available