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Synthesis and Acetylcholinesterase and Butyrylcholinesterase Inhibitory Activities of 7‐Alkoxyl Substituted Indolizinoquinoline‐5,12‐dione Derivatives
Author(s) -
Wu ZuPing,
Wu XiWei,
Shen Ting,
Li YanPing,
Cheng Xi,
Gu LianQuan,
Huang ZhiShu,
An LinKun
Publication year - 2012
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201100188
Subject(s) - butyrylcholinesterase , acetylcholinesterase , chemistry , cholinesterase , aché , selectivity , alkoxy group , stereochemistry , enzyme , biochemistry , organic chemistry , pharmacology , catalysis , alkyl , biology
Abstract A series of novel 7‐alkoxyl substituted indolizinoquinoline‐5,12‐dione derivatives were synthesized. The cholinesterase inhibition assays indicated that most synthesized compounds exhibited good activity for acetylcholinesterase (AChE) and high selectivity index of AChE over butyrylcholinesterase (BuChE). Compound 12b exhibited the most potent AChE inhibitory activity with an IC 50 value of 0.068 µM and the highest selectivity index of 144. Kinetic study of AChE indicated that a mixed type of inhibition pattern existed for these indolizinoquinoline‐5,12‐dione derivatives. Molecular docking study indicated that compound 12b could bind to both the catalytically active site and the peripheral anionic site of AChE.