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(±)-Torreyunlignans A–D, Rare 8–9′ Linked Neolignan Enantiomers as Phosphodiesterase-9A Inhibitors from Torreya yunnanensis

Author:
Cheng, Zhong-Bin, Lu, Xiao, Bao, Jing-Mei, Han, Qing-Hua, Dong, Zhen, Tang, Gui-Hua, Gan, Li-She, Luo, Hai-Bin, Yin, Sheng
Source:
Journal of natural products 2014 v.77 no.12 pp. 2651-2657
ISSN:
1520-6025
Subject:
Alzheimer disease, Torreya, adenosine, diabetes, enantiomers, inhibitory concentration 50, lignans, spectroscopy, tritium
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 ([³H]-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.
Agid:
5494237