Synthesis, Molecular Docking, and Biological Evaluation of Benzimidazole Derivatives as Selective Butyrylcholinesterase Inhibitors

Author(s): Zhe Y. Ha, Hoay C. Ong, Chuan W. Oo, Keng Y. Yeong*

Journal Name: Current Alzheimer Research

Volume 17 , Issue 13 , 2020

  Journal Home
Translate in Chinese
Become EABM
Become Reviewer
Call for Editor


Background: Benzimidazole is an interesting pharmacophore which has been extensively studied in medicinal chemistry due to its high affinity towards various enzymes and receptors. Its derivatives have been previously shown to possess a wide range of biological activities including anthelmintic, antihypertensive, antiulcer, as well as anticholinesterase activity.

Objective: The objective of this study is to search for more potent benzimidazole-based cholinesterase inhibitors, through the modification of the 1- and 2-positions of the benzimidazole core.

Methods: Synthesis of compounds were carried out via a 4-step reaction scheme following a previously reported protocol. Structure-activity relationship of the compounds are established through in vitro cholinesterase assays and in silico docking studies. Furthermore, cytotoxicity and blood brain barrier (BBB) permeability of the compounds were also investigated.

Results: Among the synthesised compounds, three of them (5IIa, 5IIb, and 5IIc) exhibited potent selective butyrylcholinesterase inhibition at low micromolar level. The compounds did not show any significant cytotoxicity when tested against a panel of human cell lines. Moreover, the most active compound, 5IIc, was highly permeable across the blood brain barrier.

Conclusion: In total 10 benzimidazole derivatives were synthesized and screened for their AChE and BuChE inhibitory activities. Lead compound 5Iic, represents a valuable compound for further development as potential AD therapeutics.

Keywords: Benzimidazoles, cholinesterase, Alzheimer’s disease, butyrylcholinesterase, blood-brain barrier, selective inhibitors.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2020
Page: [1177 - 1185]
Pages: 9
DOI: 10.2174/1567205018666210218151228
Price: $65

Article Metrics

PDF: 17