Synthesis, anticholinesterase and antioxidant potentials of ketoesters derivatives of succinimides: a possible role in the management of Alzheimer's

Abdul Sadiq; Fawad Mahmood; Farhat Ullah; Muhammad Ayaz; Sajjad Ahmad; Faizan Ul Haq; Ghazan Khan; Muhammad Saeed Jan

doi:10.1186/s13065-015-0107-2

Synthesis, anticholinesterase and antioxidant potentials of ketoesters derivatives of succinimides: a possible role in the management of Alzheimer's

Chem Cent J. 2015 May 26:9:31. doi: 10.1186/s13065-015-0107-2. eCollection 2015.

Authors

Abdul Sadiq¹, Fawad Mahmood², Farhat Ullah¹, Muhammad Ayaz¹, Sajjad Ahmad¹, Faizan Ul Haq¹, Ghazan Khan¹, Muhammad Saeed Jan¹

Affiliations

¹ Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan.
² Department of Pharmacy, University of Malakand, Chakdara, Dir Pakistan ; Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, KPK Pakistan.

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.

Keywords: Acetylcholinesterase; Alzheimer’s; Antioxidant; Ketoesters; Michael addition; Succinimides.