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Chem Biol Drug Des. 2016 Dec;88(6):889-898. doi: 10.1111/cbdd.12822. Epub 2016 Aug 17.

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

Author information

1
Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
2
Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China. qinhuali@whut.edu.cn.
3
Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
4
Department of Chemistry, University of Sargodha, Sargodha, Pakistan.
5
Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China. snab_hussaini@yahoo.com.
6
Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia. snab_hussaini@yahoo.com.

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.

KEYWORDS:

acetylcholinesterase; butyrylcholinesterase; monoamine oxidase; neurodegeneration; neuroprotection

PMID:
27434226
DOI:
10.1111/cbdd.12822
[Indexed for MEDLINE]

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