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

Authors
  • Guzel, Abdussamat1
  • Isık, Zeynep2
  • Gok, Yetkin2
  • Taskin-Tok, Tugba3, 4
  • Aktas,1
  • 1 Department of Medical Services and Techniques, Vocational School of Health Service, Inonu University, Malatya, Türkiye.
  • 2 Department of Chemistry, Faculty of Arts and Science, Inönü University, Malatya, Türkiye.
  • 3 Department of Chemistry, Faculty of Arts and Sciences, Gaziantep University, Gaziantep, Türkiye.
  • 4 Department of Bioinformatics and Computational Biology, Institute of Health Sciences, Gaziantep University, Gaziantep, Türkiye.
Type
Published Article
Journal
Current topics in medicinal chemistry
Publication Date
Jan 01, 2023
Volume
23
Issue
25
Pages
2416–2426
Identifiers
DOI: 10.2174/1568026623666230614150520
PMID: 37317917
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

This work contains the synthesis of seven new N-heterocyclic compounds bearing imidazole, benzimidazole, pyridine, and morpholine moieties. 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. 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. 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. These new syntheses are drugs that can be used as AChE inhibitors in Alzheimer's disease. Copyright© Bentham Science Publishers; For any queries, please email at [email protected].

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