Prediction of Anti-Alzheimer's Activity of Flavonoids Targeting Acetylcholinesterase in silico.
BACKGROUND
Prenylated and pyrano-flavonoids of the genus Artocarpus J. R. Forster & G. Forster are well known for their acetylcholinesterase (AChE) inhibitory, anti-cholinergic, anti-inflammatory, anti-microbial, anti-oxidant, anti-proliferative and tyrosinase inhibitory activities. Some of these compounds have also been shown to be effective against Alzheimer's disease.


OBJECTIVE
The aim of the in silico study was to establish protocols to predict the most effective flavonoid from prenylated and pyrano-flavonoid classes for AChE inhibition linking to the potential treatment of Alzheimer's disease.


METHODS
Three flavonoids isolated from Artocarpus anisophyllus Miq. were selected for the study. With these compounds, Lipinski filter, ADME/Tox screening, molecular docking and quantitative structure-activity relationship (QSAR) were performed in silico. In vitro activity was evaluated by bioactivity staining based on the Ellman's method.


RESULTS
In the Lipinski filter and ADME/Tox screening, all test compounds produced positive results, but in the target fishing, only one flavonoid could successfully target AChE. Molecular docking was performed on this flavonoid, and this compound gained the score as -13.5762. From the QSAR analysis the IC50was found to be 1659.59 nM. Again, 100 derivatives were generated from the parent compound and docking was performed. The derivative compound 20 was the best scorer, i.e. -31.6392 and IC50was predicted as 6.025 nM.


CONCLUSIONS
Results indicated that flavonoids could be efficient inhibitors of AChE and thus, could be useful in the management of Alzheimer's disease. Copyright © 2017 John Wiley & Sons, Ltd.
Department of Life Science and Bioinformatics, Assam University, Silchar, 788011, Assam, India.
Subrata
S
Das
Bioinformatics Centre, Assam University, Silchar, 788011, Assam, India.
Monjur A
MA
Laskar
Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool, L3 3AF, UK.
Satyajit D
SD
Sarker
Department of Life Science and Bioinformatics, Assam University, Silchar, 788011, Assam, India.|Bioinformatics Centre, Assam University, Silchar, 788011, Assam, India.
Manabendra D
MD
Choudhury
Department of Life Science and Bioinformatics, Assam University, Silchar, 788011, Assam, India.
Prakash Roy
PR
Choudhury
Department of Life Science and Bioinformatics, Assam University, Silchar, 788011, Assam, India.
Abhijit
A
Mitra
Chemistry Department, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia.
Shajarahtunnur
S
Jamil
Chemistry Department, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia.
Siti Mariam A
SMA
Lathiff
Chemistry Department, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia.
Siti Awanis
SA
Abdullah
Chemistry Department, Faculty of Science, Universiti Teknologi Malaysia, 81310 UTM Johor Bahru, Johor, Malaysia.
Norazah
N
Basar
Medicinal Chemistry and Natural Products Research Group, School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, James Parsons Building, Byrom Street, Liverpool, L3 3AF, UK.
Lutfun
L
Nahar
Department of Life Science and Bioinformatics, Assam University, Silchar, 788011, Assam, India.|Bioinformatics Centre, Assam University, Silchar, 788011, Assam, India.
Anupam D
http://orcid.org/0000-0001-8916-2791
AD
Talukdar
D000110:Acetylcholinesterase; D000544:Alzheimer Disease / Q000188:drug therapy*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D005419:Flavonoids; D000110:Acetylcholinesterase
ADME/Tox screening; Alzheimer's disease; Artocarpus anisophyllus; Lipinski filter; QSAR; acetylcholinesterase