Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation

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Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation Publisher

Nazari M¹ ; Rezaee E¹ ; Hariri R² ; Akbarzadeh T² ; Tabatabai SA¹

Show Affiliations

1. Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

Source: EXCLI Journal Published:2021

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. © 2021, Leibniz Research Centre for Working Environment and Human Factors. All rights reserved.

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Style	Citing Format
MLA	Nazari M, et al.. "Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation." EXCLI Journal, vol. 20, no. , 2021, pp. 907-921.
APA	Nazari M, Rezaee E, Hariri R, Akbarzadeh T, Tabatabai SA (2021). Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation. EXCLI Journal, 20(), 907-921.
Chicago	Nazari M, Rezaee E, Hariri R, Akbarzadeh T, Tabatabai SA. "Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation." EXCLI Journal 20, no. (2021): 907-921.
Harvard	Nazari M et al. (2021) 'Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation', EXCLI Journal, 20(), pp. 907-921.
Vancouver	Nazari M, Rezaee E, Hariri R, Akbarzadeh T, Tabatabai SA. Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation. EXCLI Journal. 2021;20():907-921.
BibTex	@article{ author = {Nazari M and Rezaee E and Hariri R and Akbarzadeh T and Tabatabai SA}, title = {Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation}, journal = {EXCLI Journal}, volume = {20}, number = {}, pages = {907-921}, year = {2021} }
RIS	TY - JOUR AU - Nazari M AU - Rezaee E AU - Hariri R AU - Akbarzadeh T AU - Tabatabai SA TI - Novel 1,2,4-Oxadiazole Derivatives As Selective Butyrylcholinesterase Inhibitors: Design, Synthesis, and Biological Evaluation JO - EXCLI Journal VL - 20 IS - SP - 907 EP - 921 PY - 2021 ER -

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