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J Med Chem. 2007 Nov 1;50(22):5311-23. Epub 2007 Sep 29.

New potent acetylcholinesterase inhibitors in the tetracyclic triterpene series.

Author information

1
Institut de Chimie des Substances Naturelles, Bt 27, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.

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.

PMID:
17902635
DOI:
10.1021/jm070536w
[Indexed for MEDLINE]

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