title: 2-(2-(4-Benzoylpiperazin-1-yl)ethyl)isoindoline-1,3-dione derivatives: Synthesis, docking and acetylcholinesterase inhibitory evaluation as anti-alzheimer agents.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Studied compounds could be potential leads for discovery of novel anti-Alzheimer agents in the future.
authors.affiliation: Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Pharmacology, Toxicology and Medical Services, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Mohammadi-Farani
authors.affiliation: Students Research Committee, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Nasibeh
authors.initials: N
authors.lastname: Abdi
authors.affiliation: Neurobiomedical Research Center, Yazd Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Moradi
authors.affiliation: Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Alireza
authors.initials: A
authors.lastname: Aliabadi
keywords: Acetylcholinesterase Alzheimer; Docking; Ellman test; Phthalimide; Synthesis