title: (±)-Torreyunlignans A-D, rare 8-9' linked neolignan enantiomers as phosphodiesterase-9A inhibitors from Torreya yunnanensis.
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.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University , Guangzhou, Guangdong 510006, People's Republic of China.
authors.forename: Zhong-Bin
authors.initials: ZB
authors.lastname: Cheng
authors.forename: Xiao
authors.initials: X
authors.lastname: Lu
authors.forename: Jing-Mei
authors.initials: JM
authors.lastname: Bao
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Han
authors.forename: Zhen
authors.initials: Z
authors.lastname: Dong
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Tang
authors.forename: Li-She
authors.initials: LS
authors.lastname: Gan
authors.forename: Hai-Bin
authors.initials: HB
authors.lastname: Luo
authors.forename: Sheng
authors.initials: S
authors.lastname: Yin
mesh_terms: D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects; D000242:Cyclic AMP; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000187:drug effects*; D018547:Plant Stems / Q000737:chemistry; D013237:Stereoisomerism; D032490:Taxaceae / Q000737:chemistry*
chemical_list: D004365:Drugs, Chinese Herbal; D017705:Lignans; D010726:Phosphodiesterase Inhibitors; D000242:Cyclic AMP; D010727:Phosphoric Diester Hydrolases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C116137:PDE9A protein, human