Design, synthesis and evaluation of acridone-2-carbohydrazide derivatives as p-AKT Ser473 kinase inhibitors
Aim: A series of benzylidene- and phenylethylidene-substituted acridone-2-carbohydrazide derivatives were designed, synthesized and evaluated for their cytotoxicity and response to p-AKT Ser473. Methods: The structures of the synthesized compounds were confirmed by spectroscopic techniques and evaluated for AKT enzyme inhibition activities. Molecular docking and in silico absorption, distribution, metabolism, elimination and toxicity studies were also performed. Results: Compounds 8k, 8v and 9h demonstrated good cytotoxicity against breast cancer cell lines. Especially, compounds 8v and 9h exhibited remarkable inhibition, with IC50 values of 1.75 and 2.40 μM, respectively. These compounds inhibited p-AKT Ser473 more specifically than total AKT in a dose-dependent manner. Moreover, they caused G0/G1-phase cell cycle arrest and cell apoptosis. Conclusion: This study identified compound 8v as a potent p-AKT Ser473 inhibitor.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Future medicinal chemistry - 15(2023), 8 vom: 17. Apr., Seite 699-716 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yadav, Tanuja T [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.05.2023 Date Revised 25.05.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.4155/fmc-2022-0271 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356737136 |
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| 245 | 1 | 0 | |a Design, synthesis and evaluation of acridone-2-carbohydrazide derivatives as p-AKT Ser473 kinase inhibitors |
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| 500 | |a Date Completed 18.05.2023 | ||
| 500 | |a Date Revised 25.05.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Aim: A series of benzylidene- and phenylethylidene-substituted acridone-2-carbohydrazide derivatives were designed, synthesized and evaluated for their cytotoxicity and response to p-AKT Ser473. Methods: The structures of the synthesized compounds were confirmed by spectroscopic techniques and evaluated for AKT enzyme inhibition activities. Molecular docking and in silico absorption, distribution, metabolism, elimination and toxicity studies were also performed. Results: Compounds 8k, 8v and 9h demonstrated good cytotoxicity against breast cancer cell lines. Especially, compounds 8v and 9h exhibited remarkable inhibition, with IC50 values of 1.75 and 2.40 μM, respectively. These compounds inhibited p-AKT Ser473 more specifically than total AKT in a dose-dependent manner. Moreover, they caused G0/G1-phase cell cycle arrest and cell apoptosis. Conclusion: This study identified compound 8v as a potent p-AKT Ser473 inhibitor | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a acridone-2-carbohydrazides | |
| 650 | 4 | |a anticancer | |
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| 700 | 1 | |a Bajaj, Shalini |e verfasserin |4 aut | |
| 700 | 1 | |a Yc, Mayur |e verfasserin |4 aut | |
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