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Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors

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Abstract

A new series of compounds based on benzodiazepine-1,2,3-triazole were synthesized and evaluated as cholinesterase inhibitors by Ellman’s method. The compounds proved to be selective inhibitors of butyrylcholinesterase (BuChE) over acetylcholinesterase. The most potent compound was 3,3-dimethyl-11-(3-((1-(4-nitrobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one, identified as a submicromolar inhibitor of BuChE with IC50 value of 0.2 µM. In addition, the amyloid-β self-aggregation evaluation studies for selected compounds showed potent inhibitory effects compared to donepezil. The docking and cell viability studies supported the potential of compound 9b-6 as significant BuChE inhibitor.

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Acknowledgements

This work was supported and funded by Tehran University of Medical Sciences (TUMS); Grant No. 96-01-92-34801.

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Authors and Affiliations

  1. Drug Design and Development Research Center, The Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran

    Mehrdad Mehrazar, Fereshteh Goli, Setareh Moghimi & Loghman Firoozpour

  2. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran

    Mahdi Hassankalhori

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

    Mahsa Toolabi & Alireza Foroumadi

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

    Hamid Nadri

  5. Department of Pharmaceutical Chemistry, College of Pharmacy, Jouf University, Aljouf, Sakaka, 2014, Saudi Arabia

    Syed Nasir Abbas Bukhari

  6. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Alireza Foroumadi

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  1. Mehrdad Mehrazar
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Mehrazar, M., Hassankalhori, M., Toolabi, M. et al. Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors. Mol Divers 24, 997–1013 (2020). https://doi.org/10.1007/s11030-019-10008-x

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