Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation

Gao Feng Zha, Cheng Pan Zhang, Hua Li Qin, Ibrahim Jantan, Muhammad Sher, Muhammad Wahab Amjad, Muhammad Ajaz Hussain, Zahid Hussain, Bukhari Syed Nasir Abbas

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

A series of new α,β-unsaturated carbonyl-based cyclohexanone derivatives was synthesized by simple condensation method and all compounds were characterized by using various spectroscopic techniques. New compounds were evaluated for their effects on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). These compounds were also screened for in vitro cytotoxicity and for inhibitory activity for self-induced Aβ1-42 aggregation. The effect of these compounds against amyloid β-induced cytotoxicity was also investigated. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against AChE and self-induced Aβ1-42 aggregation. The compound 3o exhibited best AChE (IC50 = 0.037 μM) inhibitory potential. Furthermore, compound 3o disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 76.6%. Compounds containing N-methyl-4-piperidone linker, showed high acetylcholinesterase and self-induced Aβ aggregation inhibitory activities as compared to reference drug donepezil. The pre-treatment of cells with synthetic compounds protected them against Aβ-induced cell death by up to 92%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment and our study suggest the cyclohexanone derivatives as promising new inhibitors for AChE and BuChE, potentially useful to treat neurodegenerative diseases.

Original languageEnglish
Pages (from-to)2352-2359
Number of pages8
JournalBioorganic and Medicinal Chemistry
Volume24
Issue number10
DOIs
Publication statusPublished - 15 May 2016

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Butyrylcholinesterase
Cholinesterase Inhibitors
Acetylcholinesterase
Amyloid
Agglomeration
Derivatives
Cytotoxicity
Piperidones
Neurodegenerative diseases
Artificial Cells
Cell death
Neurodegenerative Diseases
Inhibitory Concentration 50
Condensation
Cell Death
Cells
cyclohexanone
Pharmaceutical Preparations
Experiments
In Vitro Techniques

Keywords

  • Alzheimer's disease
  • Dementia
  • Neurodegeneration
  • Neuroprotection

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. / Zha, Gao Feng; Zhang, Cheng Pan; Qin, Hua Li; Jantan, Ibrahim; Sher, Muhammad; Amjad, Muhammad Wahab; Hussain, Muhammad Ajaz; Hussain, Zahid; Syed Nasir Abbas, Bukhari.

In: Bioorganic and Medicinal Chemistry, Vol. 24, No. 10, 15.05.2016, p. 2352-2359.

Research output: Contribution to journalArticle

Zha, Gao Feng ; Zhang, Cheng Pan ; Qin, Hua Li ; Jantan, Ibrahim ; Sher, Muhammad ; Amjad, Muhammad Wahab ; Hussain, Muhammad Ajaz ; Hussain, Zahid ; Syed Nasir Abbas, Bukhari. / Biological evaluation of synthetic α,β-unsaturated carbonyl based cyclohexanone derivatives as neuroprotective novel inhibitors of acetylcholinesterase, butyrylcholinesterase and amyloid-β aggregation. In: Bioorganic and Medicinal Chemistry. 2016 ; Vol. 24, No. 10. pp. 2352-2359.
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