Identification of AChE targeted therapeutic compounds for Alzheimer's disease: an in-silico study with DFT integration.

Autor: Rawat K; Computational Biology and Biotechnology Laboratory, Department of Botany, Soban Singh Jeena University, Almora, Uttarakhand, India., Tewari D; Department of Biotechnology, Kumaun University, Bhimtal, Uttarakhand, India., Bisht A; Department of Botany, Soban Singh Jeena University, Pt. Badridutt Pandey Campus Bageshwar, Almora, Uttarakhand, 263601, India., Chandra S; Computational Biology and Biotechnology Laboratory, Department of Botany, Soban Singh Jeena University, Almora, Uttarakhand, India. scjnu@yahoo.co.in., Tiruneh YK; Department of Biology, Biomedical Sciences stream, Bahir Dar University, P.O.Box=79, Bahir, Ethiopia. yewult82@gmail.com., Hassan HM; Department of Pathology, College of Medicine, King Khalid University, 61421, Asir, Saudi Arabia.; Department of pathology, Faculty of Medicine, Assiut University, Assiut, Egypt., Al-Emam A; Department of Pathology, College of Medicine, King Khalid University, 61421, Asir, Saudi Arabia., Sindi ER; Division of Clinical Biochemistry, Department of Basic Medical Sciences, College of Medicine, University of Jeddah, 23890, Jeddah, Saudi Arabia., Al-Dies AM; Chemistry Department, Umm Al-Qura University, Al-Qunfudah University College, Mecca, Saudi Arabia.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Dec 05; Vol. 14 (1), pp. 30356. Date of Electronic Publication: 2024 Dec 05.
DOI: 10.1038/s41598-024-81285-2
Abstrakt: Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by cognitive deterioration and changes in behavior. Acetylcholinesterase (AChE), which hydrolyzes acetylcholine, is a key drug target for treating AD. This research aimed to identify new AChE inhibitors using the IMPPAT database. We used known drugs as a basis to search for similar chemicals in the IMPPAT database and created a library of 127 plant-based compounds. Initial screening of these compounds was performed using molecular docking, followed by an analysis of their drug-likeness and ADMET properties. Compounds with favorable properties underwent density functional theory (DFT) calculations to assess their electronic properties such as HOMO-LUMO gap, electron density, and molecular orbital distribution. These descriptors provided insights into each compound's reactivity, stability, and binding potential with AChE. Promising candidates were further evaluated through molecular dynamics (MD) simulations over 100 ns and MMPBSA analysis for the last 30 ns. Two compounds, Biflavanone (IMPHY013027) with a binding free energy of - 130.394 kcal/mol and Calomelanol J (IMPHY007737) with - 107.908 kcal/mol, demonstrated strong binding affinities compared to the reference molecule HOR, which has a binding free energy of - 105.132 kcal/mol. These compounds exhibited promising drug-ability profiles in both molecular docking and MD simulations, indicating their potential as novel AChE inhibitors for AD treatment. However, further experimental validation is necessary to verify their effectiveness and safety.
Competing Interests: Declarations. Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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