Prospective acetylcholinesterase inhibitory activity of indole and its analogs

Acetylcholinesterase (AChE) inhibitory activity is one of the proposed targets for indole analogs. Simple indoles with substitution of methoxy, carboxy or hydroxy at the benzene ring showed a low percent of inhibitory activity in eel-AChE. Adding a side chain at the pyrrole ring, such as serotonin,...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2012-04, Vol.22 (8), p.2885-2888
Main Authors: Khorana, Nantaka, Changwichit, Kanokwan, Ingkaninan, Kornkanok, Utsintong, Maleeruk
Format: Article
Language:English
Subjects:
Acetylcholinesterase
Acetylcholinesterase - metabolism
Acetylcholinesterase inhibitory activity
Alzheimer’s disease
Benzene
Binding Sites
Biological and medical sciences
Carbolines - chemistry
Carbolines - pharmacology
Cholinesterase Inhibitors - chemical synthesis
Cholinesterase Inhibitors - chemistry
Cholinesterase Inhibitors - pharmacology
Conformation
Data processing
Enzyme Activation - drug effects
galantamine
Humans
Indole
Indoles
Indoles - chemical synthesis
Indoles - chemistry
Indoles - pharmacology
Medical sciences
Molecular Conformation
Neuropharmacology
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychopharmacology
pyrroles
Quinolines
Quinolines - chemistry
Quinolines - pharmacology
Serotonin
β-Carbolines
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Acetylcholinesterase (AChE) inhibitory activity is one of the proposed targets for indole analogs. Simple indoles with substitution of methoxy, carboxy or hydroxy at the benzene ring showed a low percent of inhibitory activity in eel-AChE. Adding a side chain at the pyrrole ring, such as serotonin, β-carbolines and quinolines (the bioisostere of indole), improved the inhibitory activity significantly. However, proper substitution and conformation of the ring were required for good binding. The result of inhibition in human-AChE of serotonin, β-carbolines and quinolines showed similar profile as eel-AChE with lower magnitude. The data from molecular docking showed that they shared the same binding site as galantamine.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2012.02.057