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Synthesis, characterization and investigation of AChE and BuChE inhibitory activity of 1-alkyl-4-[(5,6-dimethoxy-1-indanone-2-yl)methylene]pyridinium halide derivatives

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Abstract

The design, synthesis and characterization of a series of 1-alkyl-4-[(5,6-dimethoxy-1-indanone-2-yl)methylene]pyridinium halide derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors for the treatment of Alzheimer’s disease were reported. The strategy for this synthesis was based on aldol condensation reaction between 4-pyridinecarboxaldehyde with 5,6-dimethoxy-1-indanone in the presence of NaOH in EtOH-H2O solution as the first step and N-alkylation reaction of the produced 5,6-dimethoxy-2-[(pyridin-4-yl)methylene]-1-indanone with various alkyl halides (R–X) in the second step. This reaction was carried out under reflux temperature in polar aprotic solvents such as acetone or acetonitrile. 1H and 13C NMR and FTIR spectroscopy along with CHN analysis were used to confirm the structure of our synthesized compounds. Biological activities including acetylcholinesterase and butyrylcholinesterase (BuChE) inhibitions for synthesized compounds were tested using the Ellman method. The results were compared with donepezil and galantamine, and among the synthesized compounds, the highest inhibitory activity with BuChE IC50 = 0.55 μM was observed.

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Acknowledgements

This project was financially supported by a grant from Deputy for Research and Technology of Iranian Ministry of Health and Medical Education. The authors would like to acknowledge the financial support from Tabriz University of medical sciences and the University of Tabriz.

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Authors and Affiliations

  1. Department of Organic and Biochemistry, Faculty of Chemistry, University of Tabriz, Tabriz, Iran

    Hanieh Farrokhi, Sakineh Mozaffarnia, Keshvar Rahimpour & Reza Teimuri-Mofrad

  2. Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran

    Sakineh Mozaffarnia & Mohammad Reza Rashidi

Authors
  1. Hanieh Farrokhi
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  2. Sakineh Mozaffarnia
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  3. Keshvar Rahimpour
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  4. Mohammad Reza Rashidi
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  5. Reza Teimuri-Mofrad
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Correspondence to Mohammad Reza Rashidi or Reza Teimuri-Mofrad.

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Farrokhi, H., Mozaffarnia, S., Rahimpour, K. et al. Synthesis, characterization and investigation of AChE and BuChE inhibitory activity of 1-alkyl-4-[(5,6-dimethoxy-1-indanone-2-yl)methylene]pyridinium halide derivatives. J IRAN CHEM SOC 17, 593–600 (2020). https://doi.org/10.1007/s13738-019-01804-1

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  • DOI: https://doi.org/10.1007/s13738-019-01804-1

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