Design, synthesis, in vitro, and in vivo evaluation of novel phthalazinone‐based derivatives as promising acetylcholinesterase inhibitors for treatment of Alzheimer's disease
Abstract Twenty novel phthalazinone‐based compounds were designed as acetylcholinesterase ( h AChE) inhibitors. Compounds7e and17c demonstrated comparable or superior activity compared to donepezil, respectively, in in vitro enzyme assay. Moreover, both compounds7e and17c possess minimal toxicity on hepatic and neuroblastoma cell lines. Besides, it was proved that compounds7e and17c 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 compound17c suggested this compound as a mixed‐type inhibitor that could bind to both the peripheral (PAS) and the catalytic site (CAS) of the h AChE 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, Seite 1231-1246 |
| Beteiligte Personen: |
Ezzat, Manal Abdel Fattah [VerfasserIn] |
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| Anmerkungen: |
© 2023 Wiley Periodicals LLC. |
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| Umfang: |
16 |
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| doi: |
10.1002/ddr.22082 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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WLY015454681 |
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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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| 520 | |a Abstract Twenty novel phthalazinone‐based compounds were designed as acetylcholinesterase ( h AChE) inhibitors. Compounds7e and17c demonstrated comparable or superior activity compared to donepezil, respectively, in in vitro enzyme assay. Moreover, both compounds7e and17c possess minimal toxicity on hepatic and neuroblastoma cell lines. Besides, it was proved that compounds7e and17c 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 compound17c suggested this compound as a mixed‐type inhibitor that could bind to both the peripheral (PAS) and the catalytic site (CAS) of the h AChE enzyme. The synthesized molecules were subjected to in silico analyses, including molecular docking studies, and the outcomes were consistent with the in vitro findings. | ||
| 700 | 1 | |a Abdelhamid, Sara Mohamed |4 aut | |
| 700 | 1 | |a Fouad, Marwa A. |4 aut | |
| 700 | 1 | |a Abdel‐Aziz, Hatem A. |4 aut | |
| 700 | 1 | |a Allam, Heba Abdelrasheed |4 aut | |
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