Benzofurans from Styrax agrestis As Acetylcholinesterase Inhibitors: Structure-Activity Relationships and Molecular Modeling Studies.

Jiawei Liu , Vincent Dumontet (1) , Anne-Laure Simonin , Bogdan I Iorga (1) , Vincent Guerineau (1) , Marc Litaudon (1) , van Hung Nguyen (1) , Françoise Gueritte (1)

1 ICSN - Institut de Chimie des Substances Naturelles

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 (IC(50) 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.

Domaines: Chimie organique

Jiawei Liu, Vincent Dumontet, Anne-Laure Simonin, Bogdan I Iorga, Vincent Guerineau, et al.. Benzofurans from Styrax agrestis As Acetylcholinesterase Inhibitors: Structure-Activity Relationships and Molecular Modeling Studies.. Journal of Natural Products, 2011, 74 (10), pp.2081-8. ⟨10.1021/np200308j⟩. ⟨hal-00647691⟩