New Potent Acetylcholinesterase Inhibitors in the Tetracyclic Triterpene Series
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- 作者：Thibault Sauvaî ; tre ; Mireille Barlier ; Denyse Herlem ; Nohad Gresh ; Angè ; le Chiaroni ; Daniel Guenard ; Catherine Guillou
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：November 1, 2007
- 年：2007
- 卷：50
- 期：22
- 页码：5311 - 5323
- 全文大小：398K
- 年卷期：v.50,no.22(November 1, 2007)
- ISSN：1520-4804
文摘
A new highly selective inhibitor of acetylcholinesterase (AChE) was discovered by high-throughput screening.Compound 1 was synthesized from a natural product, the N-3-isobutyrylcycloxobuxidine-F 2. A new extractionprotocol of this compound is described. The hemisynthesis and optimization of 1 are reported. The analogsof 1 were tested in vitro for the inhibition of both cholinesterases (AChE and BuChE). These compoundsselectively inhibited AChE. Extensive molecular docking studies were performed with 2 and AChE employingDiscover Biosym software to rationalize the binding interaction. The results suggested that ligand 2 bindssimultaneously to both catalytic and peripheral sites of AChE.