Chromone derivatives bearing pyridinium moiety as multi-target-directed ligands against Alzheimer's disease
Copyright © 2021 Elsevier Inc. All rights reserved..
A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8-0.71 µM) and showed remarkable BuChE inhibition activity (IC50 = 1.9-0.006 µM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 µM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 µM) and BuChE (IC50 = 0.006 µM), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aβ-induced .neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:110 |
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| Enthalten in: |
Bioorganic chemistry - 110(2021) vom: 15. Mai, Seite 104750 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Abdpour, Shahin [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 15.10.2021 Date Revised 15.10.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2021.104750 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM322483522 |
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| 520 | |a Copyright © 2021 Elsevier Inc. All rights reserved. | ||
| 520 | |a A new serise of 7-hydroxy-chromone derivatives bearing pyridine moiety were synthesized, and evaluated as multifunctional agents against Alzheimer's disease (AD). Most of the compounds were good AChE inhibitors (IC50 = 9.8-0.71 µM) and showed remarkable BuChE inhibition activity (IC50 = 1.9-0.006 µM) compared with donepezil as the standard drug (IC50 = 0.023 and 3.4 µM). Compounds 14 and 10 showed the best inhibitory activity toward AChE (IC50 = 0.71 µM) and BuChE (IC50 = 0.006 µM), respectively. The ligand-protein docking simulations and kinetic studies revealed that compound 14 and 10 could bind effectively to the peripheral anionic binding site (PAS) of the AChE and BuChE through mixed-type inhibition. In addition, the most potent compounds showed acceptable neuroprotective activity on H2O2- and Aβ-induced .neurotoxicity in PC12 cells, more than standard drugs. The compounds could block effectively self- and AChE-induced Aβ aggregation. All the results suggest that compounds 14 and 10 could be considered as promising multi-target-directed ligands against AD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alzheimer’s disease | |
| 650 | 4 | |a Anti-amyloid aggregation | |
| 650 | 4 | |a Cholinesterase inhibitors | |
| 650 | 4 | |a Chromone | |
| 650 | 4 | |a Neuroprotective activity | |
| 650 | 4 | |a Pyridinium salts | |
| 650 | 7 | |a Cholinesterase Inhibitors |2 NLM | |
| 650 | 7 | |a Chromones |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a Pyridinium Compounds |2 NLM | |
| 650 | 7 | |a Hydrogen Peroxide |2 NLM | |
| 650 | 7 | |a BBX060AN9V |2 NLM | |
| 650 | 7 | |a Acetylcholinesterase |2 NLM | |
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| 650 | 7 | |a Butyrylcholinesterase |2 NLM | |
| 650 | 7 | |a EC 3.1.1.8 |2 NLM | |
| 700 | 1 | |a Jalili-Baleh, Leili |e verfasserin |4 aut | |
| 700 | 1 | |a Nadri, Hamid |e verfasserin |4 aut | |
| 700 | 1 | |a Forootanfar, Hamid |e verfasserin |4 aut | |
| 700 | 1 | |a Bukhari, Syed Nasir Abbas |e verfasserin |4 aut | |
| 700 | 1 | |a Ramazani, Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Ebrahimi, Seyed Esmaeil Sadat |e verfasserin |4 aut | |
| 700 | 1 | |a Foroumadi, Alireza |e verfasserin |4 aut | |
| 700 | 1 | |a Khoobi, Mehdi |e verfasserin |4 aut | |
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