Novel 1,2,4-oxadiazole derivatives as selective butyrylcholinesterase inhibitors: Design, synthesis and biological evaluation

Authors

  • Maryam Nazari Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran https://orcid.org/0000-0002-8838-0014
  • Elham Rezaee Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. No. 2660, Vali-e-Asr., Tehran 1991953381, Iran, Tel: 00982188200093; Fax: 00982188665341; E-mail: e.rezaee63@sbmu.ac.ir https://orcid.org/0000-0002-6458-0097
  • Roshanak Hariri Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Tahmineh Akbarzadeh Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
  • Sayyed Abbas Tabatabai Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. No. 2660, Vali-e-Asr., Tehran 1991953381, Iran, Tel: 00982188200093; Fax: 00982188665341; E-mail: sa_tabatabai@sbmu.ac.ir https://orcid.org/0000-0002-7363-3517

DOI:

https://doi.org/10.17179/excli2021-3569

Keywords:

Alzheimer’s disease, 1,2,4-oxadiazole, Biological evaluation, Butyrylcholinesterase inhibitor, Synthesis

Abstract

Alzheimer’s disease (AD) is a progressive mental disorder that brings a huge economic burden to the healthcare systems. During this illness, acetylcholine levels in the cholinergic systems gradually diminish, which results in severe memory loss and cognitive impairments. Moreover, Butyrylcholinesterase (BuChE) enzyme participates in cholinergic neurotransmission regulation by playing a prominent role in the latter phase of AD. In this study, based on donepezil, which is an effective acetylcholinesterase (AChE) inhibitor, a series of 1,2,4-oxadiazole compounds were designed, synthesized and their inhibitory activities towards AChE and BuChE enzymes were evaluated. Some structures exhibited a higher selectivity rate towards BuChE in comparison to donepezil. Notably, compound 6n with an IC50 value of 5.07 µM and an SI ratio greater than 19.72 showed the highest potency and selectivity towards BuChE enzyme. The docking result revealed that compound 6n properly fitted the active site pocket of BuChE enzyme, and formed desirable lipophilic interactions and hydrogen bonds. Moreover, according to in silico ADME studies, these compounds have proper potential for being developed as new oral anti-Alzheimer’s agents.

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Published

2021-05-18

How to Cite

Nazari, M., Rezaee, E., Hariri, R., Akbarzadeh, T., & Tabatabai, S. A. (2021). Novel 1,2,4-oxadiazole derivatives as selective butyrylcholinesterase inhibitors: Design, synthesis and biological evaluation. EXCLI Journal, 20, 907–921. https://doi.org/10.17179/excli2021-3569

Issue

Vol. 20 (2021)

Section

Original articles

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Copyright (c) 2021 Maryam Nazari, Elham Rezaee, Roshanak Hariri, Tahmineh Akbarzadeh, Sayyed Abbas Tabatabai

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