Prediction of Anti‐Alzheimer's Activity of Flavonoids Targeting Acetylcholinesterase in silico

Introduction 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. Methodology 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 IC50 was 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 IC50 was predicted as 6.025 nM. Conclusion 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. The authors established protocols to predict the anti‐Alzheimer's activity of flavonoids targeting acetylcholinesterase by the in silico approach. The key finding is that, the 5, 7 Dihydroxy‐4'‐methoxy‐8‐prenylflavanone a flavonoid could be an efficient inhibitor of AchE and thus, could be useful in the management of Alzheimer's disease.