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

Abstract

Prediction of anti-Alzheimer's activity of flavonoids targeting acetylcholinesterase in silico http://researchonline.ljmu.ac.uk/5218/ Article LJMU has developed LJMU Research Online for users to access the research output of the University more effectively. Copyright © and Moral Rights for the papers on this site are retained by the individual authors and/or other copyright owners. Users may download and/or print one copy of any article(s) in LJMU Research Online to facilitate their private study or for non-commercial research. You may not engage in further distribution of the material or use it for any profit-making activities or any commercial gain.The version presented here may differ from the published version or from the version of the record. Please see the repository URL above for details on accessing the published version and note that access may require a subscription. 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 pote tial treat e t of Alzhei er'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 QSAR were performed in silico. In vitro activity was evaluated by bioactivity staining ased o the Ell a 's ethod.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 number 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 Alzhei er's disease.

Computational Studies Applied to Flavonoids against Alzheimer’s and Parkinson’s Diseases

“…Das et al [112] performed in silico molecular docking studies with 5,7-dihydroxy-4′-methoxy-8-prenylflavanone (Figure 1(b)) using the FlexX of Biosolveit LeadIT program along with the drugs donepezil, galantamine, rivastigmine, tacrine, huperzine, methoxytaxine, and others. The target (PDB ID 5HF6) was chosen with the help of the PharmMapper tool (http://lilab.ecust.edu.cn) and is involved in inhibition of acetylcholinesterase.…”

Deciphering the Interactions of Bioactive Compounds in Selected Traditional Medicinal Plants against Alzheimer’s Diseases via Pharmacophore Modeling, Auto-QSAR, and Molecular Docking Approaches

“…Dhiman et al [40] developed QSAR studies utilizing a large series of flavonoid derivatives (apigenin, kaempferol, luteolin and quercetin) as monoamine oxidase inhibitors. Das et al [41] developed a QSAR model utilizing 21 known inhibitors of acetylcholinesterase. Mukesh and Dharmendra [42] reported a QSAR model for antioxidant and antimicrobial activity utilizing 18 flavonoid derivatives.…”

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“…Gene network analysis and string analysis are the two important tools in identifying the target receptor in insilico drug development process [5]. Molecular docking plays an important part in the drug discovery process as mechanism of action of the drug molecule can be identified based on inter molecular interaction among the receptor and the ligand [8]. The ligands molecule under study was taken from the LC-MS-QTOF of acetone extract of O. alismoides.…”