Synthesis, molecular docking, and biological evaluation of benzimidazole derivatives as selective butyrylcholinesterase inhibitors

Zhe Y. Ha, Hoay C. Ong, Chuan W. Oo, Keng Y. Yeong

    Research output: Contribution to journalArticleResearchpeer-review


    Benzimidazole is an interesting pharmacophore, and its derivatives have been previously shown to possess cholinesterase inhibitory activity. In this study, benzimidazole derivatives were synthesized via a 4-step reaction scheme and screened for their acetylcholinesterase and butyrylcho-linesterase inhibitory activities. Among the synthesised compounds, three of them (5IIa, 5IIb, and 5IIc) exhibited potent, selective butyrylcholinesterase inhibition at a 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. The structure-activity relationship and molecular interactions of the synthesized benzimidazole derivatives were also analysed and discussed.

    Original languageEnglish
    Pages (from-to)1177-1185
    Number of pages9
    JournalCurrent Alzheimer Research
    Issue number13
    Publication statusPublished - 2020


    • Alzheimer’s disease
    • Benzimidazoles
    • Blood-brain barrier
    • Butyrylcholinesterase
    • Cholinesterase
    • Selective inhibitors

    Cite this