1区 · 医学
Article
作者: Wang, Zhanbo ; Zhang, Menghan ; Hao, Chenyan ; Jin, Yuqing ; Ding, Yushi ; Zhang, Dayong ; Ming, Liqin ; Sun, Yuanyuan ; Xu, Kang ; You, Linjun ; Tang, Xinying ; Mao, Wenhao ; Yu, Fei ; Lu, Xiaolin ; Jiang, Jingwei ; Gao, Mengkang ; Zhang, Min ; Yang, Yong ; Tan, Jun ; Gu, Lujun ; Gu, Congying ; Ren, Xiameng
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.
