Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Bioorg Chem ; 67: 1-8, 2016 08.
Article in English | MEDLINE | ID: mdl-27231829

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 89.5µM for EeAChE and 153.8µM for EqBuChE, (2a) was identified as a second hit with an IC50 of 108.4µM (EeAChE) and 277.8µM (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.


Subject(s)
Alzheimer Disease/drug therapy , Azepines/pharmacology , Cholinesterase Inhibitors/pharmacology , Cholinesterases/metabolism , Isoquinolines/pharmacology , Molecular Docking Simulation , Alzheimer Disease/enzymology , Azepines/chemical synthesis , Azepines/chemistry , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/chemistry , Dose-Response Relationship, Drug , Humans , Isoquinolines/chemical synthesis , Isoquinolines/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Structure-Activity Relationship
SELECTION OF CITATIONS
SEARCH DETAIL