In-silico study of some natural plant phyto-compounds for the identification of novel potent cholinesterase inhibitors against Alzheimer's Disease

Dilip Kumar ,Sanjana Bhagat Sanjana Bhagat

doi:10.30574/wjarr.2021.12.3.0543

Abstract

The main aim of this study is to identify inhibitory binding potent of the available commercially alkaloids, against the crystal structure of acetylcholinesterase (AChE) protein by in silico studies. The inhibitory data of the compounds should be compared with the internal ligand as well as standard AChE inhibitor Aricept (which is used for the treatment of all stages of Alzheimer’s disease). AutoDock 4.0 is used for the docking study, conformational orientation site analysis, and, with the help of docking, we have calculated parameters like binding energy and inhibition constant. Docking's study showed that Glabridin, Isorosmanol, Quercetin, Honokiol, Eckol, Sargaquinoic acid, and Ginsedosides revealed strong binding affinity with the enzyme. Moreover, The ADMET profiling and physicochemical properties of the selected compounds are evaluated using the Molinspiration and Data warrior software. By showing a strong binding affinity value, positive bioactivity score, and good pharmacokinetic properties, the top compound was determined. After evaluation with all parameters, the compound Glabridin and Ginsedosides show the most potent inhibitory effect towards the acetylcholinesterase, so this compound could be used as a novel is required to treat Alzheimer's disease.

Highlights

Alzheimer's disease is the most prevalent progressive neurodegenerative condition, which is considered by low concentration amount of neurotransmitter, oxidative stress, and neuroinflammatory are all symptoms of Alzheimer's disease (AD) [1]
Molecular Docking Analysis The natural alkaloids and terpenoids are Glabridin, Isorosmanol, Quercetin, Honokiol, Eckol, Sargaquinoic acid, and Ginsenosides, which are generally found in various types of medicinal and dietary sources, comprise several pharmacophoric characteristics which are applicable as a drug-like moiety
Orientation of these compounds overlaps the native E2020 ligand (ARICEPT) has shown significant overlaps and similarities in binding orientation and interaction (Figure 3). These similarities have cleared that all seven phytocompounds can act as potent inhibitors of acetylcholinesterase

Summary

Introduction

Alzheimer's disease is the most prevalent progressive neurodegenerative condition, which is considered by low concentration amount of neurotransmitter (acetylcholine), oxidative stress, and neuroinflammatory are all symptoms of Alzheimer's disease (AD) [1]. Most effective treatment methods focus on activating the cholinergic receptors in the brain to improve cholinergic function, increase the concentration level of acetylcholine (Ach), to avoid breakdown by cholinesterase enzyme and other inflammatory agents [2]. ACh is the main neurotransmitter present in the central nervous systems, autonomic ganglia, different organs with the autonomic transmission, the neuromuscular junction, and synapses, ach is predominantly found in between two neurons, and have found in the vital long-axon part of cholinergic pathways. Ach is come from the nerve into the synaptic cleft part of the neuro-junction and binds to the Ach receptors (nicotinic and muscarine) present on the post-synaptic membrane, transmit the signal from the nerve. AChE is present in the different types of conducting tissue such as nerve and muscle, sensory and motor fibers, peripheral and central tissue, and cholinergic and noncholinergic fibers.

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