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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
22
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pubmed:dateCreated |
2007-10-25
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pubmed:abstractText |
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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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
50
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5311-23
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pubmed:meshHeading |
pubmed-meshheading:17902635-Acetylcholinesterase,
pubmed-meshheading:17902635-Animals,
pubmed-meshheading:17902635-Benzoxazines,
pubmed-meshheading:17902635-Binding Sites,
pubmed-meshheading:17902635-Butyrylcholinesterase,
pubmed-meshheading:17902635-Catalytic Domain,
pubmed-meshheading:17902635-Cattle,
pubmed-meshheading:17902635-Cholinesterase Inhibitors,
pubmed-meshheading:17902635-Crystallography, X-Ray,
pubmed-meshheading:17902635-Electrophorus,
pubmed-meshheading:17902635-Heterocyclic Compounds with 4 or More Rings,
pubmed-meshheading:17902635-Humans,
pubmed-meshheading:17902635-Models, Molecular,
pubmed-meshheading:17902635-Molecular Structure,
pubmed-meshheading:17902635-Species Specificity,
pubmed-meshheading:17902635-Structure-Activity Relationship,
pubmed-meshheading:17902635-Torpedo,
pubmed-meshheading:17902635-Triterpenes
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pubmed:year |
2007
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pubmed:articleTitle |
New potent acetylcholinesterase inhibitors in the tetracyclic triterpene series.
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pubmed:affiliation |
Institut de Chimie des Substances Naturelles, Bt 27, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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