Article pubs.acs.org/jnp
(±)-Torreyunlignans A−D, Rare 8−9′ Linked Neolignan Enantiomers as Phosphodiesterase-9A Inhibitors from Torreya yunnanensis Zhong-Bin Cheng,†,§ Xiao Lu,†,§ Jing-Mei Bao,† Qing-Hua Han,† Zhen Dong,† Gui-Hua Tang,† Li-She Gan,*,‡ Hai-Bin Luo,*,† and Sheng Yin*,† †
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People’s Republic of China College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
‡
S Supporting Information *
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.
T
screening program aimed at the discovery of novel PDE inhibitors from natural resources,8−11 a fraction of the ethanolic extract of T. yunnanensis showed inhibitory activity of 43% toward PDE9 and no obvious activity against PDE4 (
(±)-Torreyunlignans A−D, Rare 8−9′ Linked Neolignan Enantiomers as Phosphodiesterase-9A Inhibitors from Torreya yunnanensis Zhong-Bin Cheng,†,§ Xiao Lu,†,§ Jing-Mei Bao,† Qing-Hua Han,† Zhen Dong,† Gui-Hua Tang,† Li-She Gan,*,‡ Hai-Bin Luo,*,† and Sheng Yin*,† †
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, Guangdong 510006, People’s Republic of China College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, People’s Republic of China
‡
S Supporting Information *
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.
T
screening program aimed at the discovery of novel PDE inhibitors from natural resources,8−11 a fraction of the ethanolic extract of T. yunnanensis showed inhibitory activity of 43% toward PDE9 and no obvious activity against PDE4 (
