2. Academic Validation
  3. Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma

Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma

  • J Med Chem. 2024 Feb 20. doi: 10.1021/acs.jmedchem.3c02241.
Menghan Zhang 1,  Yushi Ding 2,  Mengkang Gao 3,  Xiaolin Lu 4,  Jun Tan 4,  Fei Yu 1,  Congying Gu 4,  Lujun Gu 1,  Xiameng Ren 1,  Chenyan Hao 4,  Liqin Ming 4,  Kang Xu 4,  Wenhao Mao 1,  Yuqing Jin 1,  Min Zhang 2,  Linjun You 2 5,  Zhanbo Wang 2 5,  Yuanyuan Sun 6,  Jingwei Jiang 6,  Yong Yang 1 7 8,  Dayong Zhang 4,  Xinying Tang 1
Affiliations

Affiliations

  • 1 School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, China 211112.
  • 2 Institute of Pharmaceutical Sciences, China Pharmaceutical University, Nanjing, China 211112.
  • 3 School of Pharmacy, China Pharmaceutical University, Nanjing, China 211112.
  • 4 School of Science, China Pharmaceutical University, Nanjing, China 211112.
  • 5 Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing, China 211112.
  • 6 Shuangyun BioMed Sci & Tech (Suzhou) Co., Ltd, Suzhou, China 215000.
  • 7 State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, China 211112.
  • 8 School of Pharmacy, Xuzhou Medical University, Xuzhou, China 221004.
PMID: 38377560 DOI: 10.1021/acs.jmedchem.3c02241
Abstract

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.

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