Molecular docking study and ADMET prediction of phytoconstituents of Withania Somniferra Flem. in Alzheimer's disease: an insilico explorative study. (20th December 2022)

• Record Type: Journal Article
• Authors: Medhi, Bikash; Prajapat, Manisha
• Is Part Of: Alzheimer's & dementia. Volume 18(2022)Supplement 10
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-20
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.065519
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: Withania somniferra Flem . (brahmi) is known for its neuroprotective property and protective action against AD. Among different phytochemicals of WS, which phytoconstituents is responsible for this neuroprotection in AD is unknown. Method: Protein Preparation, Ligand Preparation, Molecular Docking on PDB structure of target proteins GSK‐3 beta, CDK‐5, NMDA, SORLA/SORL1, P2×7R, beta catenin, sTLR5 from protein data bank were performed using Schrodinger maestro 12 Ligand preparation: Compound was retrieved from pubchem Withaferin‐A and withanolide‐A. Molecular Docking: All in silico calculations and procedures were carried out using Schrödinger software Maestro suite 2019, on an Acer predator laptop with an operating system consisting Linux Ubuntu OS 18.04.02 LTS platform. Pharmacokinetics properties of ligands: admetSAR server (http://lmmd.ecust.edu.cn:8000/) (19), AMDETlabs server (admet.scbdd.com/) and SwissADME server (www.swissadme.ch/) (21) were used for evaluation of pharmacokinetic properties of the ligands (absorption, distribution, metabolism, excretion and toxicity). Result: Out of these 30 ligands, Withaferin‐A (binding energy to the inhibitory domain of gsk3 beta and beta catenin is ‐5.135, ‐7.764 respectively and withanolide‐A binding energy to the inhibitory domain of gsk3 beta and beta catenin is ‐4.371, ‐6.946 and Both the ligands showed good binding profile, favorable pharmacokinetic profile, no violation of drug ability rules. Both the ligands showed permeability through blood brain barrier. Both the ligands shown non Ames toxicity, non carcinogen and weak inhibitor of HERG. Phytochemical of WS (Withaferin‐A and withanolide‐A) showed good binding profile against gsk3beta targets in AD. Conclusion: Phytochemical of WS (Withaferin‐A and withanolide‐A) showed good binding profile against Gsk3beta AND Beta catenin targets in AD. We need further studies to evaluate individual efficacy of these phytochemicals in different settings (in‐vitro and in‐vivo).