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New potent acetylcholinesterase inhibitors in the tetracyclic triterpene series.

Authors
  • Sauvaître, Thibault
  • Barlier, Mireille
  • Herlem, Denyse
  • Gresh, Nohad
  • Chiaroni, Angèle
  • Guenard, Daniel
  • Guillou, Catherine
Type
Published Article
Journal
Journal of medicinal chemistry
Publication Date
Nov 01, 2007
Volume
50
Issue
22
Pages
5311–5323
Identifiers
PMID: 17902635
Source
Medline
License
Unknown

Abstract

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 extraction protocol of this compound is described. The hemisynthesis and optimization of 1 are reported. The analogs of 1 were tested in vitro for the inhibition of both cholinesterases (AChE and BuChE). These compounds selectively inhibited AChE. Extensive molecular docking studies were performed with 2 and AChE employing Discover Biosym software to rationalize the binding interaction. The results suggested that ligand 2 binds simultaneously to both catalytic and peripheral sites of AChE.

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