Linked Life Data

20677317

Source:http://linkedlifedata.com/resource/pubmed/id/20677317

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2010-9-6
pubmed:abstractText
A large series of substituted coumarins linked through an appropriate spacer to 3-hydroxy-N,N-dimethylanilino or 3-hydroxy-N,N,N-trialkylbenzaminium moieties were synthesized and evaluated as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The highest AChE inhibitory potency in the 3-hydroxy-N,N-dimethylanilino series was observed with a 6,7-dimethoxy-3-substituted coumarin derivative, which, along with an outstanding affinity (IC(50)=0.236 nM) exhibits excellent AChE/BChE selectivity (SI>300 000). Most of the synthesized 3-hydroxy-N,N,N-trialkylbenzaminium salts display an AChE affinity in the sub-nanomolar to picomolar range along with excellent AChE/BChE selectivities (SI values up to 138 333). The combined use of docking and molecular dynamics simulations permitted us to shed light on the observed structure-affinity and structure-selectivity relationships, to detect two possible alternative binding modes, and to assess the critical role of pi-pi stacking interactions in the AChE peripheral binding site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1860-7187
pubmed:author
pubmed:issnType
Electronic
pubmed:day
3
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1616-30
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Design, synthesis, and biological evaluation of coumarin derivatives tethered to an edrophonium-like fragment as highly potent and selective dual binding site acetylcholinesterase inhibitors.
pubmed:affiliation
Dipartimento Farmaco-chimico, Università degli Studi di Bari Aldo Moro, via Orabona 4, 70125 Bari, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't