Designing Second Generation Anti-Alzheimer Compounds as Inhibitors of Human Acetylcholinesterase: Computational Screening of Synthetic Molecules and Dietary Phytochemicals

PloS One
Hafsa Amat-Ur-Rasool, Mehboob Ahmed

Abstract

Alzheimer's disease (AD), a big cause of memory loss, is a progressive neurodegenerative disorder. The disease leads to irreversible loss of neurons that result in reduced level of acetylcholine neurotransmitter (ACh). The reduction of ACh level impairs brain functioning. One aspect of AD therapy is to maintain ACh level up to a safe limit, by blocking acetylcholinesterase (AChE), an enzyme that is naturally responsible for its degradation. This research presents an in-silico screening and designing of hAChE inhibitors as potential anti-Alzheimer drugs. Molecular docking results of the database retrieved (synthetic chemicals and dietary phytochemicals) and self-drawn ligands were compared with Food and Drug Administration (FDA) approved drugs against AD as controls. Furthermore, computational ADME studies were performed on the hits to assess their safety. Human AChE was found to be most approptiate target site as compared to commonly used Torpedo AChE. Among the tested dietry phytochemicals, berberastine, berberine, yohimbine, sanguinarine, elemol and naringenin are the worth mentioning phytochemicals as potential anti-Alzheimer drugs The synthetic leads were mostly dual binding site inhibitors with two binding subunits linked ...Continue Reading

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Citations

Jan 24, 2017·International Journal of Biological Macromolecules·Badar Ul Islam, Shams Tabrez
Aug 21, 2019·Central Nervous System Agents in Medicinal Chemistry·Anurag K SinghGiriraj T Kulkarni
Feb 6, 2021·Brain Sciences·Hafsa Amat-Ur-RasoolWayne G Carter
Nov 19, 2020·Biomolecules·Hafsa Amat-Ur-RasoolWayne G Carter
Mar 9, 2018·European Journal of Pharmacology·Mohammad-Reza Khajevand-KhazaeiMehrdad Roghani
Jul 23, 2021·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Shanoo SuroowanMohamad Fawzi Mahomoodally
Aug 29, 2021·Phytochemistry·Toktam AkaberiMaryam Akaberi

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Methods Mentioned

BETA
X-ray

Software Mentioned

PyMOL
ALADYN
Phyre2 Homology AnalogY Recognition Engine
EMBOSS
Clustal Omega
PatchDock
Needle
PSI
FATCAT
BLAST

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