Design, synthesis, in vitro, and in vivo evaluation of novel phthalazinone-based derivatives as promising acetylcholinesterase inhibitors for treatment of Alzheimer's disease
© 2023 Wiley Periodicals LLC..
Twenty novel phthalazinone-based compounds were designed as acetylcholinesterase (hAChE) inhibitors. Compounds 7e and 17c demonstrated comparable or superior activity compared to donepezil, respectively, in in vitro enzyme assay. Moreover, both compounds 7e and 17c possess minimal toxicity on hepatic and neuroblastoma cell lines. Besides, it was proved that compounds 7e and 17c have percentage alternations and a transfer latency time comparable to donepezil and can alleviate the cognitive impairment caused by the scopolamine-induced model in mice. The kinetic analysis for compound 17c suggested this compound as a mixed-type inhibitor that could bind to both the peripheral (PAS) and the catalytic site (CAS) of the hAChE enzyme. The synthesized molecules were subjected to in silico analyses, including molecular docking studies, and the outcomes were consistent with the in vitro findings.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:84 |
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| Enthalten in: |
Drug development research - 84(2023), 6 vom: 01. Sept., Seite 1231-1246 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ezzat, Manal Abdel Fattah [VerfasserIn] |
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| Links: |
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| Themen: |
8SSC91326P |
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| Anmerkungen: |
Date Completed 13.09.2023 Date Revised 20.09.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/ddr.22082 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM357455495 |
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| 245 | 1 | 0 | |a Design, synthesis, in vitro, and in vivo evaluation of novel phthalazinone-based derivatives as promising acetylcholinesterase inhibitors for treatment of Alzheimer's disease |
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| 500 | |a published: Print-Electronic | ||
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| 520 | |a © 2023 Wiley Periodicals LLC. | ||
| 520 | |a Twenty novel phthalazinone-based compounds were designed as acetylcholinesterase (hAChE) inhibitors. Compounds 7e and 17c demonstrated comparable or superior activity compared to donepezil, respectively, in in vitro enzyme assay. Moreover, both compounds 7e and 17c possess minimal toxicity on hepatic and neuroblastoma cell lines. Besides, it was proved that compounds 7e and 17c have percentage alternations and a transfer latency time comparable to donepezil and can alleviate the cognitive impairment caused by the scopolamine-induced model in mice. The kinetic analysis for compound 17c suggested this compound as a mixed-type inhibitor that could bind to both the peripheral (PAS) and the catalytic site (CAS) of the hAChE enzyme. The synthesized molecules were subjected to in silico analyses, including molecular docking studies, and the outcomes were consistent with the in vitro findings | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a acetylcholinesterase inhibitor | |
| 650 | 4 | |a in vivo study | |
| 650 | 4 | |a phthalazine derivative | |
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| 700 | 1 | |a Abdelhamid, Sara Mohamed |e verfasserin |4 aut | |
| 700 | 1 | |a Fouad, Marwa A |e verfasserin |4 aut | |
| 700 | 1 | |a Abdel-Aziz, Hatem A |e verfasserin |4 aut | |
| 700 | 1 | |a Allam, Heba Abdelrasheed |e verfasserin |4 aut | |
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