title: Synthesis, anticholinesterase and antioxidant potentials of ketoesters derivatives of succinimides: a possible role in the management of Alzheimer's.
abstract: BACKGROUND
  Based on the pharmacological potency and structural features of succinimides, this study was designed to synthesize new ketoesters derivatives of succinimides. Furthermore, the synthesized compounds were evaluated for their possible anticholinesterase and antioxidant potentials. The compounds were synthesized by organocatalytic Michael additions of α-ketoesters to N-aryl maleimides. Acetyl and butyrylcholinesterase inhibitory activities were determined using Ellman's spectrophotometric assay. The antioxidant activity was performed with DPPH and ABTS free radicals scavenging assay.
  
  
  RESULTS
  The Michael additions of α-ketoesters to maleimides was promoted by 8-hydroxyquinoline. The organocatalyst (8-hydroxyquinoline, 20 mol %) produced the compounds in relatively shorter time (20-24 h) and with excellent isolated yields (84-98 %). The synthesized compounds (1-4) showed outstanding acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory potentials, i.e., 98.75 and 90.00 % respectively for compound 2, with IC50 < 0.1 μg/mL. Additionally, compounds 1-4 revealed moderate antioxidant activity at different concentrations. In DPPH free radical scavenging assay, compound 1 showed dominant result with 72.41 ± 0.45, 52.49 ± 0.78 and 35.60 ± 0.75 % inhibition at concentrations of 1000, 500 and 250 μg/mL respectively, IC50 value of 440 μg/mL. However, the free radical scavenging was better when used ABTS free radicals. In ABTS free radicals scavenging assay compound 1 exhibited 88.51 ± 0.62 % inhibition at highest tested concentration i.e., 1000 μg/mL.
  
  
  CONCLUSIONS
  Herein, we have synthesized four ketoesters derivatives of succinimides in a single step reaction and high yields. As a highlight, we have showed a first report on the anticholinesterase and antioxidant potentials of succinimides. All the compounds showed overwhelming enzyme inhibitions and moderate antioxidant potentials. Graphical AbstractGraphical representation of synthesis, anticholinesterase and antioxidant potentials of ketoester derivatives of succinimides.
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
authors.forename: Abdul
authors.initials: A
authors.lastname: Sadiq
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan ; Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK Pakistan.
authors.forename: Fawad
authors.initials: F
authors.lastname: Mahmood
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
authors.forename: Farhat
authors.initials: F
authors.lastname: Ullah
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ayaz
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
authors.forename: Sajjad
authors.initials: S
authors.lastname: Ahmad
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
authors.forename: Faizan Ul
authors.initials: FU
authors.lastname: Haq
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
authors.forename: Ghazan
authors.initials: G
authors.lastname: Khan
authors.affiliation: Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
authors.forename: Muhammad Saeed
authors.initials: MS
authors.lastname: Jan
keywords: Acetylcholinesterase; Alzheimer’s; Antioxidant; Ketoesters; Michael addition; Succinimides