PHARMASPIRE - Volume 15, Issue 02, 2023, April- June

Pages: 61-69

Date of Publication: 06-Sep-2023

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Molecular docking analysis of substituted 2-(1-benzylpiperidin-4-yl)-5-phenoxy-1H-benzo[d] imidazole derivatives as acetylcholinesterase inhibitors for the management of Alzheimer’s disease

Author: Abhimannu Shome, Pooja A. Chawla

Category: P'Ceutical Chemistry

Abstract:

The loss of cholinergic neurons in the brain and hippocampus is the hallmark of Alzheimer’s disease (AD). The hydrolyzing enzyme acetylcholinesterase (AChE) has been identified as a potential treatment for AD. One of the most significant scaffolds for AChE binding is benzyl piperidine, which is included in the medication donepezil. Along with benzimidazole, early investigations have also shown to significantly inhibit AChE. This study includes in designing of a hybrid of benzyl piperidine and benzimidazole as AChE inhibitors. The study revealed that B24, A24, and B8 showed the highest blood–brain barrier (BBB) permeability and binding affinities (?11.4 kcal/mol, 11.0 kcal/mol, and 11.1 kcal/mol, respectively). All the chemicals behaved similarly in the binding pocket of AChE. These important interactions between residues include those between Trp86, Tyr341, Ser293, and others. To stop the BBB from penetrating, polar substitutions on more than two locations were also identified. However, compound B24 is an exception. The series’ most potent ligands may be further evaluated biologically.

Keywords: Acetylcholinesterase, Alzheimer’s disease, Benzimidazole, Benzyl piperidine, Molecular docking

DOI: 10.56933/Pharmaspire.2023.15111

DOI URL: https://doi.org/10.56933/Pharmaspire.2023.15111

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