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

Mehrdad Mehrazar, Mahdi Hassankalhori, Mahsa Toolabi, Fereshteh Goli, Setareh Moghimi, Hamid Nadri, Syed Nasir Abbas Bukhari, Loghman Firoozpour, Alireza Foroumadi

Research output: Contribution to journalArticle

Abstract

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. Graphic abstract: [Figure not available: see fulltext.].

Original languageEnglish
JournalMolecular Diversity
DOIs
Publication statusAccepted/In press - 1 Jan 2019

Fingerprint

Butyrylcholinesterase
Triazoles
Benzodiazepines
inhibitors
Agglomeration
Cells
Derivatives
synthesis
Diagnostic Self Evaluation
cholinesterase
Cholinesterase Inhibitors
Acetylcholinesterase
Amyloid
Inhibitory Concentration 50
Cell Survival
viability
evaluation

Keywords

  • 1,2,3-Triazole
  • Alzheimer’s disease
  • Benzodiazepine
  • Butyrylcholinesterase inhibitor
  • Click chemistry

ASJC Scopus subject areas

  • Catalysis
  • Information Systems
  • Molecular Biology
  • Drug Discovery
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

Mehrazar, M., Hassankalhori, M., Toolabi, M., Goli, F., Moghimi, S., Nadri, H., ... Foroumadi, A. (Accepted/In press). Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors. Molecular Diversity. https://doi.org/10.1007/s11030-019-10008-x

Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors. / Mehrazar, Mehrdad; Hassankalhori, Mahdi; Toolabi, Mahsa; Goli, Fereshteh; Moghimi, Setareh; Nadri, Hamid; Bukhari, Syed Nasir Abbas; Firoozpour, Loghman; Foroumadi, Alireza.

In: Molecular Diversity, 01.01.2019.

Research output: Contribution to journalArticle

Mehrazar, M, Hassankalhori, M, Toolabi, M, Goli, F, Moghimi, S, Nadri, H, Bukhari, SNA, Firoozpour, L & Foroumadi, A 2019, 'Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors', Molecular Diversity. https://doi.org/10.1007/s11030-019-10008-x
Mehrazar, Mehrdad ; Hassankalhori, Mahdi ; Toolabi, Mahsa ; Goli, Fereshteh ; Moghimi, Setareh ; Nadri, Hamid ; Bukhari, Syed Nasir Abbas ; Firoozpour, Loghman ; Foroumadi, Alireza. / Design and synthesis of benzodiazepine-1,2,3-triazole hybrid derivatives as selective butyrylcholinesterase inhibitors. In: Molecular Diversity. 2019.
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