Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors
Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC50 = 0.054 ± 0.004 μM; MAO-B: IC50 = 3.25 ± 0.20 μM), moderate inhibitory effects on self-mediated amyloid-β (Aβ) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Future medicinal chemistry - 15(2023), 20 vom: 08. Okt., Seite 1823-1841 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hu, Zhaoxin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 14.11.2023 Date Revised 14.11.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0206 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM363940413 |
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| 245 | 1 | 0 | |a Design, synthesis and biological evaluation of novel indanones derivatives as potent acetylcholinesterase/monoamine oxidase B inhibitors |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 14.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: Based on a multitarget design strategy, a series of novel indanone-1-benzyl-1,2,3,6-tetrahydropyridin hybrids were identified for the potential treatment of Alzheimer's disease (AD). Results: These compounds exhibited significant inhibitory activities against acetylcholinesterase (AChE) and moderate inhibitory activities toward monoamine oxidase B (MAO-B). The optimal compound A1 possessed excellent dual AChE/MAO-B inhibition both in terms of potency (AChE: IC50 = 0.054 ± 0.004 μM; MAO-B: IC50 = 3.25 ± 0.20 μM), moderate inhibitory effects on self-mediated amyloid-β (Aβ) aggregation and antioxidant activity. In addition, compound A1 exhibited low neurotoxicity. More importantly, compound A1 showed significant cognitive and spatial memory improvements in the scopolamine-induced AD mouse model. Conclusion: All results suggest that compound A1 may become a promising lead of anti-AD drug for further development | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a AChE | |
| 650 | 4 | |a Alzheimer's disease | |
| 650 | 4 | |a MAO-B | |
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| 650 | 4 | |a indan-1-one | |
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| 650 | 7 | |a Amyloid beta-Peptides |2 NLM | |
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| 650 | 7 | |a Monoamine Oxidase |2 NLM | |
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| 650 | 7 | |a Monoamine Oxidase Inhibitors |2 NLM | |
| 700 | 1 | |a Zhou, Shengnan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Junda |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xinnan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Yang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Zheying |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jinyi |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jie |e verfasserin |4 aut | |
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