title: Benzofurans from Styrax agrestis as acetylcholinesterase inhibitors: structure-activity relationships and molecular modeling studies.
abstract: An extract of Styrax agrestis fruits, collected in Vietnam, significantly inhibited acetylcholinesterase (AChE) in vitro. Bioassay-guided fractionation revealed three new egonol-type benzofurans: egonol-9(Z),12(Z) linoleate (1), 7-demethoxyegonol-9(Z),12(Z) linoleate (2), and 7-demethoxyegonol oleate (4). Ten known egonol-type benzofurans were also isolated (3, 5, 6-13). In order to better understand structure-activity relationships in this series, egonol derivatives 14-19 were prepared by chemical modifications and evaluated for their inhibition of AChE, butyrylcholinesterase (BChE), and AChE-induced Aβ aggregation. Compounds 1-4 were the most potent inhibitors of the series, which exhibited inhibitory activity against AChE (IC50 1.4-3.1 μM) and, for 1, Aβ aggregation (77.6%). Molecular docking studies were also performed to investigate interaction of these compounds with the active site of AChE.
authors.affiliation: Research Center of Medicinal Plants Resource Science and Engineering, Guangzhou University of Chinese Medicine, 232 Waihuandong Road, Higher Education Mega Center, Guangzhou 510006, People's Republic of China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Liu
authors.forename: Vincent
authors.initials: V
authors.lastname: Dumontet
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Simonin
authors.forename: Bogdan I
authors.initials: BI
authors.lastname: Iorga
authors.forename: Vincent
authors.initials: V
authors.lastname: Guerineau
authors.forename: Marc
authors.initials: M
authors.lastname: Litaudon
authors.forename: Van Hung
authors.initials: VH
authors.lastname: Nguyen
authors.forename: Françoise
authors.initials: F
authors.lastname: Gueritte
mesh_terms: D001572:Benzofurans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D005638:Fruit / Q000737:chemistry; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D032362:Styrax / Q000737:chemistry*; D014744:Vietnam
chemical_list: C568753:7-demethoxyegonol oleate; C568755:7-demethoxyegonol-9(Z),12(Z) linoleate; D001572:Benzofurans; D002800:Cholinesterase Inhibitors; C568754:egonol-9(Z),12(Z) linoleate