۲-(۲-(۴-Benzoylpiperazin-۱-yl)ethyl)isoindoline-۱,۳-dione derivatives: Synthesis, docking and acetylcholinesterase inhibitory evaluation as anti-alzheimer agents
Publish place: Iranian Journal of Basic Medical Sciences، Vol: 20، Issue: 1
Publish Year: 1396
نوع سند: مقاله ژورنالی
زبان: English
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شناسه ملی سند علمی:
JR_IJBMS-20-1_010
تاریخ نمایه سازی: 28 مهر 1400
Abstract:
Objective(s): Alzheimer’s disease (AD) as progressive cognitive decline and the most common form of dementia is due to degeneration of the cholinergic neurons in the brain. Therefore, administration of the acetylcholinesterase (AChE) inhibitors such as donepezil is the first choice for treatment of the AD. In the present study, we focused on the synthesis and anti-cholinesterase evaluation of new donepezil like analogs. Materials and Methods: A new series of phthalimide derivatives (compounds ۴a-۴j) were synthesized via Gabriel protocol and subsequently amidation reaction was performed using various benzoic acid derivatives. Then, the corresponding anti-acetylcholinesterase activity of the prepared derivatives (۴a-۴j) was assessed by utilization of the Ellman's test and obtained results were compared to donepezil. Besides, docking study was also carried out to explore the likely in silico binding interactions. Results: According to the obtained results, electron withdrawing groups (Cl, F) at position ۳ and an electron donating group (methoxy) at position ۴ of the phenyl ring enhanced the acetylcholinesterase inhibitory activity. Compound ۴e (m-Fluoro, IC۵۰ = ۷.۱ nM) and ۴i (p-Methoxy, IC۵۰ = ۲۰.۳ nM) were the most active compounds in this series and exerted superior potency than donepezil (۴۱۰ nM). Moreover, a similar binding mode was observed in silico for all ligands in superimposition state with donepezil into the active site of acetylcholinesterase. Conclusion: Studied compounds could be potential leads for discovery of novel anti-Alzheimer agents in the future.
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Authors
Ahmad Mohammadi-Farani
Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
Nasibeh Abdi
Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran
Alireza Moradi
Neurobiomedical Research Center, Yazd Shahid Sadoughi University of Medical Sciences, Yazd, Iran
Alireza Aliabadi
Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran
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