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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29 Citations (Scopus)


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 & Medicinal Chemistry
Issue number8
Publication statusPublished - 1 May 2018


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

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