Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma
Targeting tumor stemness is an innovative approach to cancer treatment. Zinc Finger Protein 207 (ZNF207) is a promising target for weakening the stemness of glioma cells. Here, a series of novel N-(anthracen-9-ylmethyl) benzamide derivatives against ZNF207 were rationally designed and synthesized. The inhibitory activity was evaluated, and their structure-activity relationships were summarized. Among them, C16 exhibited the most potent inhibitory activity, as evidenced by its IC50 values ranging from 0.5-2.5 μM for inhibiting sphere formation and 0.5-15 μM for cytotoxicity. Furthermore, we found that C16 could hinder tumorigenesis and migration and promote apoptosis in vitro. These effects were attributed to the downregulation of stem-related genes. The in vivo evaluation demonstrated that C16 exhibited efficient permeability across the blood-brain barrier and potent efficacy in both subcutaneous and orthotopic glioma tumor models. Hence, C16 may serve as a potential lead compound targeting ZNF207 and has promising therapeutic potential for glioma.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:67 |
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| Enthalten in: |
Journal of medicinal chemistry - 67(2024), 5 vom: 14. März, Seite 3909-3934 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zhang, Menghan [VerfasserIn] |
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| Links: |
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| Themen: |
Antineoplastic Agents |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1021/acs.jmedchem.3c02241 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM368675807 |
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| 245 | 1 | 0 | |a Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma |
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| 520 | |a Targeting tumor stemness is an innovative approach to cancer treatment. Zinc Finger Protein 207 (ZNF207) is a promising target for weakening the stemness of glioma cells. Here, a series of novel N-(anthracen-9-ylmethyl) benzamide derivatives against ZNF207 were rationally designed and synthesized. The inhibitory activity was evaluated, and their structure-activity relationships were summarized. Among them, C16 exhibited the most potent inhibitory activity, as evidenced by its IC50 values ranging from 0.5-2.5 μM for inhibiting sphere formation and 0.5-15 μM for cytotoxicity. Furthermore, we found that C16 could hinder tumorigenesis and migration and promote apoptosis in vitro. These effects were attributed to the downregulation of stem-related genes. The in vivo evaluation demonstrated that C16 exhibited efficient permeability across the blood-brain barrier and potent efficacy in both subcutaneous and orthotopic glioma tumor models. Hence, C16 may serve as a potential lead compound targeting ZNF207 and has promising therapeutic potential for glioma | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Benzamides |2 NLM | |
| 650 | 7 | |a Antineoplastic Agents |2 NLM | |
| 650 | 7 | |a ZNF207 protein, human |2 NLM | |
| 650 | 7 | |a Microtubule-Associated Proteins |2 NLM | |
| 700 | 1 | |a Ding, Yushi |e verfasserin |4 aut | |
| 700 | 1 | |a Gao, Mengkang |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Xiaolin |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Yu, Fei |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Congying |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Lujun |e verfasserin |4 aut | |
| 700 | 1 | |a Ren, Xiameng |e verfasserin |4 aut | |
| 700 | 1 | |a Hao, Chenyan |e verfasserin |4 aut | |
| 700 | 1 | |a Ming, Liqin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Kang |e verfasserin |4 aut | |
| 700 | 1 | |a Mao, Wenhao |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Yuqing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Min |e verfasserin |4 aut | |
| 700 | 1 | |a You, Linjun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Zhanbo |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Yuanyuan |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Jingwei |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Yong |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dayong |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Xinying |e verfasserin |4 aut | |
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