Linked Life Data

21397996

Source:http://linkedlifedata.com/resource/pubmed/id/21397996

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2011-3-28
pubmed:abstractText
The leading mechanistic theory of Alzheimer's disease (AD) is the "amyloid hypothesis" which states that the accumulation of the amyloid ? protein (A?), and its subsequent aggregation into plaques, is responsible for the initiation of a cascade of events resulting in neurodegeneration and dementia. The anti-amyloid disease-modifying approach, based on the decrease in the production of A?, gained thus a paramount importance. The aim of this study was the design and synthesis of a new series of acetylcholinesterase inhibitors (AChEIs) endowed with anti-A? aggregating capability. These dual binding inhibitors, being able to interact both with the peripheral anionic site (PAS) of AChE and the catalytic subsite, proved to be able to inhibit the AChE-induced A? aggregation. Thus, starting from the lead compound 1, an AChEI composed by a benzophenone scaffold and a N,N'-methylbenzylamino group, a substantial modification aimed at targeting the PAS was performed. To this aim, different amino-terminal side chains were incorporated into this main framework, in order to mimic the diethylmethylammonium alkyl moiety of the pure PAS ligand propidium. The synthesized compounds proved to effectively and selectively inhibit AChE. Moreover, compounds 16a-c and 18a,b, with a propoxy and a hexyloxy tether respectively, showed a good activity against the AChE-induced A? aggregation. In particular, molecular modeling studies confirmed that compounds carrying the diethylaminopropoxy and the diethylaminohexyloxy side chains (compounds 16a and 19a, respectively) could suitably contact the PAS pocket of the enzyme.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1768-3254
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 Elsevier Masson SAS. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1682-93
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Benzophenone-based derivatives: a novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation.
pubmed:affiliation
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro 6, 40126 Bologna, Italy. federica.belluti@unibo.it
pubmed:publicationType
Journal Article