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Current Topics in Medicinal Chemistry

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ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

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Research Article

N-Heterocyclic Compounds, In silico Molecular Docking Studies, and In vitro Enzyme Inhibition Effect against Acetylcholinesterase Inhibitors

Author(s): Abdussamat Guzel*, Zeynep Isık, Yetkin Gok, Tugba Taskin-Tok and Aydın Aktas

Volume 23, Issue 25, 2023

Published on: 05 July, 2023

Page: [2416 - 2426] Pages: 11

DOI: 10.2174/1568026623666230614150520

Price: $65

Abstract

Background: This work contains the synthesis of seven new N-heterocyclic compounds bearing imidazole, benzimidazole, pyridine, and morpholine moieties.

Objectives: We aimed to synthesize N-heterocyclic compounds for a more effective drug candidate to increase the amount of acetylcholine in synapses in Alzheimer's disease. All compounds were characterized by 1H NMR, 13C NMR, FTIR and elemental analysis. Enzyme inhibition activity of all compounds against acetylcholinesterase was investigated, which is an indirect treatment for Alzheimer's. Molecular docking was applied to estimate the binding energy of these compounds to the acetylcholinesterase.

Methods: All compounds were synthesized from reactions of 2 equivalents of N-heterocyclic starting material and 1 equivalent of 4,4'-bis(chloromethyl)-1,1'-biphenyl. The inhibition parameters of IC50 and Ki were calculated by the spectrophotometric method. AutoDock4 was used to define the binding pose of the compounds.

Results: Ki values were found in the range of 80.03 ± 19.64 to 5014.98 ± 1139.60 nM for AChE as an enzyme inhibition strategy, which is an important parameter for the treatment of neurodegenerative such as Alzheimer's disease. In this study, molecular docking is exerted to predict the binding energy of heterocyclic compounds (especially 2, 3, and 5) against acetylcholinesterase enzyme. Their docking binding energies are in good agreement with experimental findings.

Conclusion: These new syntheses are drugs that can be used as AChE inhibitors in Alzheimer's disease.

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