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Publication Type : Journal Article
Source : Royal Society of Chemistry
Url : https://pubs.rsc.org/en/content/articlehtml/2023/ra/d3ra00526g
Campus : Kochi
School : School of Pharmacy
Year : 2023
Abstract : Alzheimer's disease (AD), a neurodegenerative condition associated with ageing, can occur. AD gradually impairs memory and cognitive function, which leads to abnormal behavior, incapacity, and reliance. By 2050, there will likely be 100 million cases of AD in the world's population. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibition are significant components of AD treatment. This work developed models using the genetic method multiple linear regression, atom-based, field-based, and 3-D pharmacophore modelling. Due to internal and external validation, all of the models have solid statistical (R2 > 0.81 and Q2 > 0.77) underpinnings. From a pre-plated CNS library (6055), we discovered a hit compound using virtual screening on a QSAR model. Through molecular docking, additional hit compounds were investigated (XP mode). Finally, a molecular dynamics simulation revealed that the Molecule5093-4BDS complex was stable (100 ns). Finally, the expected ADME properties for the hit compounds (Molecule5093, Molecule1076, Molecule4412, Molecule1053, and Molecule3344) were found. According to the results of our investigation and the prospective hit compounds, BuChE inhibitors may be used as a treatment for AD.
Cite this Research Publication : Kumar S, Manoharan A, Jayan J, Abdelgawad MA, Mahdi WA, Alshehri S, Ghoneim MM, Pappachen LK, Zachariah SM, Aneesh TP, Mathew B., Exploiting butyrylcholinesterase inhibitors through a combined 3-D pharmacophore modeling, QSAR, molecular docking, and molecular dynamics investigation, RSC Adv. 2023 Mar 23;13(14):9513-9529. doi:10.1039/d3ra00526g. Erratum in: RSC Adv, 2023.