2-(2-(4-Benzoylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives: Synthesis, docking and acetylcholinesterase inhibitory evaluation as anti-alzheimer agents | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 10، دوره 20، شماره 1، فروردین 2017، صفحه 59-66 اصل مقاله (1.36 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2017.8095 | ||
| نویسندگان | ||
| Ahmad Mohammadi-Farani1، 2؛ Nasibeh Abdi3، 4؛ Alireza Moradi5؛ Alireza Aliabadi* 1، 4 | ||
| 1Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| 2Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| 3Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| 4Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran | ||
| 5Neurobiomedical Research Center, Yazd Shahid Sadoughi University of Medical Sciences, Yazd, Iran | ||
| چکیده | ||
| 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 4a-4j) 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 (4a-4j) 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 3 and an electron donating group (methoxy) at position 4 of the phenyl ring enhanced the acetylcholinesterase inhibitory activity. Compound 4e (m-Fluoro, IC50 = 7.1 nM) and 4i (p-Methoxy, IC50 = 20.3 nM) were the most active compounds in this series and exerted superior potency than donepezil (410 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. | ||
| کلیدواژهها | ||
| Acetylcholinesterase Alzheimer؛ Docking؛ Ellman test؛ Phthalimide؛ Synthesis | ||
| مراجع | ||
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