title: Synthetic conversion of ACAT inhibitor to acetylcholinesterase inhibitor.
abstract: Natural product acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor pyripyropene A was synthetically converted to acetylcholinesterase (AChE) inhibitor via heterolitic cleavage of the 2-pyrone ring, followed by gamma-acylation/cyclization with several aroyl chlorides. The 4-pyridyl analogue selectively showed AChE inhibitory activity (IC50 7.9 microM) and no ACAT inhibitory activity IC50 = >1000 microM.
authors.affiliation: Research Center for Biological Function, The Kitasato Institute and Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Obata
authors.forename: T
authors.initials: T
authors.lastname: Sunazuka
authors.forename: K
authors.initials: K
authors.lastname: Otoguro
authors.forename: H
authors.initials: H
authors.lastname: Tomoda
authors.forename: Y
authors.initials: Y
authors.lastname: Harigaya
authors.forename: S
authors.initials: S
authors.lastname: Omura
mesh_terms: D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
chemical_list: D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D002785:Sterol O-Acyltransferase