Arylacryl amides : Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF-κB pathway
Copyright © 2024 Elsevier Inc. All rights reserved..
Arylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK2 cells. Furthermore, 9d can interact with TLR4 to inhibit TLR4/STING/NF-κB pathway in the RAW264.7 cell. In vivo AKI mice model, 9d significantly downregulated the level of serum creatinine (Scr), blood urea nitrogen (BUN) and the inflammatory factors (IL-1β, IL-6, TNF-α) to improve kidney function. Morphological and KIM-1 analyses showed that 9d alleviated cisplatin-induced tubular damage. In a word, 9d was a promising lead compound for preventive and therapeutic of AKI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:146 |
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| Enthalten in: |
Bioorganic chemistry - 146(2024) vom: 26. Apr., Seite 107303 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Xiaoming [VerfasserIn] |
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| Links: |
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| Themen: |
Acute kidney injury |
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| Anmerkungen: |
Date Completed 15.04.2024 Date Revised 15.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bioorg.2024.107303 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM370105702 |
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| 520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
| 520 | |a Arylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK2 cells. Furthermore, 9d can interact with TLR4 to inhibit TLR4/STING/NF-κB pathway in the RAW264.7 cell. In vivo AKI mice model, 9d significantly downregulated the level of serum creatinine (Scr), blood urea nitrogen (BUN) and the inflammatory factors (IL-1β, IL-6, TNF-α) to improve kidney function. Morphological and KIM-1 analyses showed that 9d alleviated cisplatin-induced tubular damage. In a word, 9d was a promising lead compound for preventive and therapeutic of AKI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute kidney injury | |
| 650 | 4 | |a Arylacryl amide | |
| 650 | 4 | |a Cisplatin | |
| 650 | 4 | |a Hydroxybenzotriazole | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Proliferation | |
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| 650 | 7 | |a Cisplatin |2 NLM | |
| 650 | 7 | |a Q20Q21Q62J |2 NLM | |
| 650 | 7 | |a Toll-Like Receptor 4 |2 NLM | |
| 650 | 7 | |a Tumor Necrosis Factor-alpha |2 NLM | |
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| 700 | 1 | |a Li, Ziyun |e verfasserin |4 aut | |
| 700 | 1 | |a Rong, Kuanrong |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Shan |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Yun |e verfasserin |4 aut | |
| 700 | 1 | |a Zuo, Jiawei |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Wenjian |e verfasserin |4 aut | |
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