Synthetic conversion of ACAT inhibitor to acetylcholinesterase inhibitor.
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.
Obata
R
R
Research Center for Biological Function, The Kitasato Institute and Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
Sunazuka
T
T
Otoguro
K
K
Tomoda
H
H
Harigaya
Y
Y
Omura
S
S
D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*
D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D002785:Sterol O-Acyltransferase