Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease

Jing Leng, Hua Li Qin, Kaicheng Zhu, Ibrahim Jantan, Muhammad Ajaz Hussain, Muhammad Sher, Muhammad Wahab Amjad, Muhammad Naeem-ul-Hassan, Waqas Ahmad, Bukhari Syed Nasir Abbas

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Neurodegeneration, a complex disease state, comprises several pathways that contribute to cell death. Conventional approach of targeting only one of these pathways has not been proven to be entirely successful and has demanded a hypothetical change as to how researchers design and develop new drugs. In this study, effects of a series of α, β-unsaturated carbonyl-based tetralone derivatives against Alzheimer's disease (AD) were investigated. Moreover, their activity toward amyloid β-induced cytotoxicity was also studied. Six compounds including 3f, 3o, 3u, 3ae, 3af, and 3ag were discovered to be most protective against Aβ-induced neuronal cell death in PC12 cells. The findings of in vitro experiment revealed that most of these compounds exhibited potent inhibitory activity against MAO-B, AChE, and self-induced Aβ1-42 aggregation. The compound 3f exhibited best AChE (IC50 = 0.045 ± 0.02 μm) inhibitory potential in addition to potent inhibition of MAO-B (IC50 = 0.88 ± 0.12 μm). Furthermore, compound 3f disassembled the Aβ fibrils produced by self-induced Aβ aggregation by 78.2 ± 4.8%. Collectively, these findings suggest that some compounds from this series have potential to be promising multifunctional agents for AD treatment.

Original languageEnglish
JournalChemical Biology and Drug Design
DOIs
Publication statusAccepted/In press - 2016

Fingerprint

Tetralones
Monoamine Oxidase
Inhibitory Concentration 50
Alzheimer Disease
Cell Death
Cell death
Derivatives
PC12 Cells
Agglomeration
Amyloid
Research Personnel
Cytotoxicity
Pharmaceutical Preparations
Experiments

Keywords

  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Monoamine oxidase
  • Neurodegeneration
  • Neuroprotection

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine

Cite this

Leng, J., Qin, H. L., Zhu, K., Jantan, I., Hussain, M. A., Sher, M., ... Syed Nasir Abbas, B. (Accepted/In press). Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease. Chemical Biology and Drug Design. https://doi.org/10.1111/cbdd.12822

Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease. / Leng, Jing; Qin, Hua Li; Zhu, Kaicheng; Jantan, Ibrahim; Hussain, Muhammad Ajaz; Sher, Muhammad; Amjad, Muhammad Wahab; Naeem-ul-Hassan, Muhammad; Ahmad, Waqas; Syed Nasir Abbas, Bukhari.

In: Chemical Biology and Drug Design, 2016.

Research output: Contribution to journalArticle

Leng, J, Qin, HL, Zhu, K, Jantan, I, Hussain, MA, Sher, M, Amjad, MW, Naeem-ul-Hassan, M, Ahmad, W & Syed Nasir Abbas, B 2016, 'Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease', Chemical Biology and Drug Design. https://doi.org/10.1111/cbdd.12822
Leng, Jing ; Qin, Hua Li ; Zhu, Kaicheng ; Jantan, Ibrahim ; Hussain, Muhammad Ajaz ; Sher, Muhammad ; Amjad, Muhammad Wahab ; Naeem-ul-Hassan, Muhammad ; Ahmad, Waqas ; Syed Nasir Abbas, Bukhari. / Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease. In: Chemical Biology and Drug Design. 2016.
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