In silico studies, synthesis and pharmacological evaluation to explore multi-targeted approach for imidazole analogues as potential cholinesterase inhibitors with neuroprotective role for Alzheimer's disease

Archana S. Gurjar, Mrunali N. Darekar, Keng Yoon Yeong, Luyi Ooi

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    17 Citations (Scopus)

    Abstract

    Alzheimer's disease (AD) is a progressive neurodegenerative disorder with multiple factors associated with its pathogenesis. Our strategy against AD involves design of multi-targeted 2-substituted-4,5-diphenyl-1H-imidazole analogues which can interact and inhibit AChE, thereby, increasing the synaptic availability of ACh, inhibit BuChE, relieve induced oxidative stress and confer a neuroprotective role. Molecular docking was employed to study interactions within the AChE active site. In silico ADME study was performed to estimate pharmacokinetic parameters. Based on computational studies, some analogues were synthesized and subjected to pharmacological evaluation involving antioxidant activity, toxicity and memory model studies in animals followed by detailed mechanistic in vitro cholinesterase inhibition study. Amongst the series, analogue 13 and 20 are the most promising multi-targeted candidates which can potentially increase memory, decrease free radical levels and protect neurons against cognitive deficit.

    Original languageEnglish
    Pages (from-to)1511-1522
    Number of pages12
    JournalBioorganic and Medicinal Chemistry
    Volume26
    Issue number8
    DOIs
    Publication statusPublished - 1 May 2018

    Keywords

    • 2-Substituted-4,5-diphenyl-1H-imidazole
    • Acetylcholinesterase
    • In vitro antioxidant assay
    • In vitro Ellman assay
    • Molecular docking

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