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 language | English |
|---|---|
| Journal | Chemical Biology and Drug Design |
| DOIs | |
| Publication status | Accepted/In press - 2016 |
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Keywords
- Acetylcholinesterase
- Butyrylcholinesterase
- Monoamine oxidase
- Neurodegeneration
- Neuroprotection
ASJC Scopus subject areas
- Biochemistry
- Molecular Medicine
Cite this
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 journal › Article
}
TY - JOUR
T1 - Evaluation of multifunctional synthetic tetralone derivatives for treatment of Alzheimer's disease
AU - Leng, Jing
AU - Qin, Hua Li
AU - Zhu, Kaicheng
AU - Jantan, Ibrahim
AU - Hussain, Muhammad Ajaz
AU - Sher, Muhammad
AU - Amjad, Muhammad Wahab
AU - Naeem-ul-Hassan, Muhammad
AU - Ahmad, Waqas
AU - Syed Nasir Abbas, Bukhari
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Acetylcholinesterase
KW - Butyrylcholinesterase
KW - Monoamine oxidase
KW - Neurodegeneration
KW - Neuroprotection
UR - http://www.scopus.com/inward/record.url?scp=84982239399&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84982239399&partnerID=8YFLogxK
U2 - 10.1111/cbdd.12822
DO - 10.1111/cbdd.12822
M3 - Article
C2 - 27434226
AN - SCOPUS:84982239399
JO - Chemical Biology and Drug Design
JF - Chemical Biology and Drug Design
SN - 1747-0277
ER -