Synthesis and molecular docking studies of 5-trifluoromethoxy-2-indolinones as cholinesterase dual inhibitors
Background: In Alzheimer's disease, butyrylcholinesterase (BuChE) activity gradually increases, while acetylcholinesterase (AChE) activity decreases or remains unchanged. Dual inhibitors have important roles in regulation of synaptic acetylcholine levels and progression of Alzheimer's disease. Methods: 1-(Thiomorpholin-4-ylmethyl)/benzyl-5-trifluoromethoxy-2-indolinones (6-7) were synthesized. AChE and BuChE inhibitory effects were investigated with Ellman's method. Molecular docking studies were performed for analyzing the possible binding interactions at active sites. Results: Compound 6g was the strongest inhibitor against both AChE (Ki = 0.35 μM) and BuChE (Ki = 0.53 μM). It showed higher inhibitory effects than both donepezil and galantamine. Moreover, compound 7m had a higher inhibitory effect than galantamine and the effect was comparable to that of donepezil against both AChE (Ki = 0.69 μM) and BuChE (Ki = 0.95 μM). Conclusion: The benzyl substitution compared with 1-(thiomorpholin-4-ylmethyl) group significantly increased both AChE and BuChE inhibitory effects.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:16 |
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| Enthalten in: |
Future medicinal chemistry - 16(2024), 7 vom: 12. März, Seite 623-645 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Soylu-Eter, Özge [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 13.03.2024 Date Revised 13.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2023-0281 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369599829 |
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| 245 | 1 | 0 | |a Synthesis and molecular docking studies of 5-trifluoromethoxy-2-indolinones as cholinesterase dual inhibitors |
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| 500 | |a Date Revised 13.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Background: In Alzheimer's disease, butyrylcholinesterase (BuChE) activity gradually increases, while acetylcholinesterase (AChE) activity decreases or remains unchanged. Dual inhibitors have important roles in regulation of synaptic acetylcholine levels and progression of Alzheimer's disease. Methods: 1-(Thiomorpholin-4-ylmethyl)/benzyl-5-trifluoromethoxy-2-indolinones (6-7) were synthesized. AChE and BuChE inhibitory effects were investigated with Ellman's method. Molecular docking studies were performed for analyzing the possible binding interactions at active sites. Results: Compound 6g was the strongest inhibitor against both AChE (Ki = 0.35 μM) and BuChE (Ki = 0.53 μM). It showed higher inhibitory effects than both donepezil and galantamine. Moreover, compound 7m had a higher inhibitory effect than galantamine and the effect was comparable to that of donepezil against both AChE (Ki = 0.69 μM) and BuChE (Ki = 0.95 μM). Conclusion: The benzyl substitution compared with 1-(thiomorpholin-4-ylmethyl) group significantly increased both AChE and BuChE inhibitory effects | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a 5-trifluoromethoxy-2-indolinones | |
| 650 | 4 | |a acetylcholinesterase inhibitors | |
| 650 | 4 | |a butyrylcholinesterase inhibitors | |
| 650 | 4 | |a hydrazinecarbothioamide | |
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