Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors: Characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity

Bukhari Syed Nasir Abbas, Ibrahim Jantan, Vijay H. Masand, Devidas T. Mahajan, Muhammad Sher, M. Naeem-Ul-Hassan, Muhammad Wahab Amjad

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

A series of novel carbonyl compounds was synthesized by a simple, eco-friendly and efficient method. These compounds were screened for anti-oxidant activity, in vitro cytotoxicity and for inhibitory activity for acetylcholinesterase and butyrylcholinesterase. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. Among them, compound 14 exhibited strong free radical scavenging activity (18.39 μM) while six compounds (1, 3, 4, 13, 14, and 19) were found to be the most protective against Aβ-induced neuronal cell death in PC12 cells. Compounds 4 and 14, containing N-methyl-4-piperidone linker, showed high acetylcholinesterase inhibitory activity as compared to reference drug donepezil. Molecular docking and QSAR (Quantitative Structure-Activity Relationship) studies were also carried out to determine the structural features that are responsible for the acetylcholinesterase and butyrylcholinesterase inhibitory activity.

Original languageEnglish
Pages (from-to)355-365
Number of pages11
JournalEuropean Journal of Medicinal Chemistry
Volume83
DOIs
Publication statusPublished - 18 Aug 2014

Fingerprint

Butyrylcholinesterase
Molecular modeling
Quantitative Structure-Activity Relationship
Cholinesterase Inhibitors
Acetylcholinesterase
Cytotoxicity
Amyloid
Piperidones
Carbonyl compounds
PC12 Cells
Scavenging
Cell death
Oxidants
Free Radicals
Cell Death
Pharmaceutical Preparations

Keywords

  • 4-Piperidone
  • Alzheimer's disease
  • Neuroprotection
  • Oxidative stress
  • Synthesis

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors : Characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity. / Syed Nasir Abbas, Bukhari; Jantan, Ibrahim; Masand, Vijay H.; Mahajan, Devidas T.; Sher, Muhammad; Naeem-Ul-Hassan, M.; Amjad, Muhammad Wahab.

In: European Journal of Medicinal Chemistry, Vol. 83, 18.08.2014, p. 355-365.

Research output: Contribution to journalArticle

Syed Nasir Abbas, Bukhari ; Jantan, Ibrahim ; Masand, Vijay H. ; Mahajan, Devidas T. ; Sher, Muhammad ; Naeem-Ul-Hassan, M. ; Amjad, Muhammad Wahab. / Synthesis of α, β-unsaturated carbonyl based compounds as acetylcholinesterase and butyrylcholinesterase inhibitors : Characterization, molecular modeling, QSAR studies and effect against amyloid β-induced cytotoxicity. In: European Journal of Medicinal Chemistry. 2014 ; Vol. 83. pp. 355-365.
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