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Synthesis, docking study, and biological evaluation of novel umbellipherone/hymecromone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors

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Abstract

A novel hybrid series of umbellipherone and benzyl amine scaffolds, linked via triazole ring, was synthesized and evaluated as both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitors. Most of the synthesized compounds showed moderate to high activities by using Ellman’s modified assay. Among the target compounds, 6e bearing 3-methoxy substituent on benzyl moiety was the most active one (AChE and BuChE IC50 = 3.4 and 1.1 μM, respectively). Finally, binding modes of the target compound was studied using molecular docking stimulations. The neuroprotectivity evaluation exhibited that this compound efficiently protected PC12 neurons against H2O2-induced cell death.

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Acknowledgements

This work was supported by grants from the Research Council of Tehran University of Medical Sciences and Iran National Science Foundation (INSF).

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Faculty of Pharmacy,, Shahid Sadoughi University of Medical Sciences,, Yazd,, Iran

    Alireza Moradi, Hamid Nadri & Bahar Pakseresht

  2. The Institute of Pharmaceutical Sciences (TIPS),, Tehran University of Medical Sciences,, Tehran,, Iran

    Laleh Faraji, Zeinab Hasanpour, Mostafa Golshani, Setareh Moghimi, Loghman Firoozpour & Mehdi Khoobi

  3. Department of Cellular Biotechnology at Cell Science Research Center, Royan Institute for Biotechnology,, ACECR,, Isfahan,, Iran

    Farshad H Moghadam

  4. Department of Chemistry,, University of Zanjan,, P.O. Box 45195-313,, Zanjan,, Iran

    Ali Ramazani

  5. Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy,, Tehran University of Medical Sciences,, Tehran,, Iran

    Mehdi Khoobi

  6. Department of Medicinal Chemistry, Faculty of Pharmacy,, Tehran University of Medical Sciences,, Tehran,, Iran

    Alireza Foroumadi

  7. Department of Medicinal Chemistry, Faculty of Pharmacy and Neuroscience Research Center,, Institute of Neuropharmacology, Kerman University of Medical Sciences,, Kerman,, Iran

    Alireza Foroumadi

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  1. Alireza Moradi
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  2. Laleh Faraji
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  3. Hamid Nadri
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  4. Zeinab Hasanpour
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  5. Farshad H Moghadam
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  12. Alireza Foroumadi
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Correspondence to Mehdi Khoobi.

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Moradi, A., Faraji, L., Nadri, H. et al. Synthesis, docking study, and biological evaluation of novel umbellipherone/hymecromone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors. Med Chem Res 27, 1741–1747 (2018). https://doi.org/10.1007/s00044-018-2187-8

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  • DOI: https://doi.org/10.1007/s00044-018-2187-8

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