Abstract
(±)-Torreyunlignans A-D (1a/1b-4a/4b), four pairs of new 8-9' linked neolignan enantiomers featuring a rare (E)-2-styryl-1,3-dioxane moiety, were isolated from the trunk of Torreya yunnanensis. The structures were determined by combined spectroscopic and chemical methods, and the absolute configurations were elucidated by ECD calculations. The compounds were screened by using tritium-labeled adenosine 3',5'-cyclic monophosphate ([(3)H]-cGMP) as a substrate for inhibitory affinities against phosphodiesterase-9A (PDE9A), which is a potential target for the treatment of diabetes and Alzheimer's disease. All of the enantiomers exhibited inhibition against PDE9A with IC50 values ranging from 5.6 to 15.0 μM. This is the first report of PDE9A inhibitors from nature.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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3',5'-Cyclic-AMP Phosphodiesterases / drug effects
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Cyclic AMP
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Drugs, Chinese Herbal* / chemistry
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Drugs, Chinese Herbal* / isolation & purification
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Drugs, Chinese Herbal* / pharmacology
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Lignans* / chemistry
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Lignans* / isolation & purification
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Lignans* / pharmacology
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Phosphodiesterase Inhibitors* / chemistry
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Phosphodiesterase Inhibitors* / isolation & purification
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Phosphodiesterase Inhibitors* / pharmacology
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Phosphoric Diester Hydrolases / drug effects*
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Plant Stems / chemistry
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Stereoisomerism
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Taxaceae / chemistry*
Substances
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Drugs, Chinese Herbal
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Lignans
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Phosphodiesterase Inhibitors
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Cyclic AMP
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Phosphoric Diester Hydrolases
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3',5'-Cyclic-AMP Phosphodiesterases
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PDE9A protein, human