Synthesis and Evaluation of Anti-acetylcholinesterase Activity of 2-(2-(4-(2-Oxo-2-phenylethyl)piperazin-1-yl) ethyl)Isoindoline-1,3-dione Derivatives with Potential Anti-Alzheimer Effects

Document Type: Original Article

Authors

1 1Novel Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran 2Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

2 3Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran

3 1Novel Drug Delivery Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.4Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran

4 2Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran5Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran

Abstract

 




Objective(s): Alzheimer's disease (AD) is a neurodegenerative disorder in elderly patients. Decrease in cholinergic neurotransmission is the main known cause in the pathophysiology of the disease. Improvement and potentiation of the cholinergic system could be beneficial for treatment of the AD. Acetylcholinesterase inhibitors such as donepezil can enhance the duration of action of acetylcholine (Ach) and therefore, through this mechanism improve the symptoms of AD. Materials and Methods: In the current study, based on the potential inhibitory activity of phthalimide derivatives towards acetylcholinesterase enzyme, a new series of phthalimide-based compounds were synthesized (4a-4e) and anti-acetylcholinesterase effect was assessed using Ellman's test. Compound 4b with 4-Fluorophenyl moiety was the most potent derivative in this series (IC50
= 16.42 ± 1.07 μM). It was shown that, none of the synthesized compounds showed superior inhibitory potency compared to donepezil (0.41 ± 0.09 μM) as a reference drug.
 
Conclusion:
The new synthesized phthalimide based analogs could function as potential acetylcholinesterase inhibitors. Further studies are necessary for development of potent analogs.

Keywords


 

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