3-Aryl Coumarin Derivatives Bearing Aminoalkoxy Moiety as Multi-Target-Directed Ligands against Alzheimer's Disease
© 2019 Wiley-VHCA AG, Zurich, Switzerland..
Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross-linker are investigated in acetyl- and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3-(3,4-Dichlorophenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50 =0.27 μm). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed-type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks β-amyloid (Aβ) self-aggregation with a ratio of 44.11 % at 100 μm and significantly protects PC12 cells from H2 O2 -damage in a dose-dependent manner.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Chemistry & biodiversity - 16(2019), 5 vom: 03. Mai, Seite e1800436 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abdshahzadeh, Helia [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 31.05.2019 Date Revised 31.05.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/cbdv.201800436 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM295794917 |
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| 520 | |a © 2019 Wiley-VHCA AG, Zurich, Switzerland. | ||
| 520 | |a Two series of novel coumarin derivatives, substituted at 3 and 7 positions with aminoalkoxy groups, are synthesized, characterized, and screened. The effect of amine substituents and the length of cross-linker are investigated in acetyl- and butyrylcholinesterase (AChE and BuChE) inhibition. Target compounds show moderate to potent inhibitory activities against AChE and BuChE. 3-(3,4-Dichlorophenyl)-7-[4-(diethylamino)butoxy]-2H-chromen-2-one (4y) is identified as the most potent compound against AChE (IC50 =0.27 μm). Kinetic and molecular modeling studies affirmed that compound 4y works in a mixed-type way and interacts simultaneously with the catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. In addition, compound 4y blocks β-amyloid (Aβ) self-aggregation with a ratio of 44.11 % at 100 μm and significantly protects PC12 cells from H2 O2 -damage in a dose-dependent manner | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a synthesis design | |
| 650 | 4 | |a β-amyloid | |
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