Please use this identifier to cite or link to this item: http://hdl.handle.net/10174/19808

Title: New cholinesterase inhibitors for Alzheimer's disease: Structure Activity Studies (SARs) and molecular docking of isoquinolone and azepanone derivatives
Authors: Bacalhau, P
Caldeira, Teresa
Martins, Rosário
Burke, Anthony
Editors: Distefano, MD
Keywords: Medicinal
síntese
Issue Date: 14-May-2016
Publisher: Elsevier
Abstract: A library of isoquinolinone and azepanone derivatives were screened for both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity. The strategy adopted included (a) in vitro biological assays, against eel AChE (EeAChE) and equine serum BuChE (EqBuChE) in order to determine the compounds IC50 and their dose-response activity, consolidated by (b) molecular docking studies to evaluate the docking poses and interatomic interactions in the case of the hit compounds, validated by STD-NMR studies. Compound (1f) was identified as one of these hits with an IC50 of 89.5 mu M for EeAChE and 153.8 mu M for EqBuChE, (2a) was identified as a second hit with an IC50 of 108.4 mu M (EeAChE) and 277.8 mu M (EqBuChE). In order to gain insights into the binding mode and principle active site interactions of these molecules, (R)-(1f) along with 3 other analogues (also as the R-enantiomer) were docked into both RhAChE and hBuChE models. Galantamine was used as the benchmark. The docking study was validated by performing an STD-NMR study of (1f) with EeAChE using galantamine as the benchmark.
URI: http://www.sciencedirect.com/science/article/pii/S0045206816300463
http://hdl.handle.net/10174/19808
ISSN: 1090-2120
Type: article
Appears in Collections:CQE - Publicações - Artigos em Revistas Internacionais Com Arbitragem Científica

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