Journal of medicinal chemistry · 2024
Discovery of Novel N-(Anthracen-9-ylmethyl) Benzamide Derivatives as ZNF207 Inhibitors Promising in Treating Glioma.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Zhang Menghan, Ding Yushi, Gao Mengkang, Lu Xiaolin, Tan Jun, Yu Fei, Gu Congying, Gu Lujun, Ren Xiameng, Hao Chenyan, Ming Liqin, Xu Kang, Mao Wenhao, Jin Yuqing, Zhang Min, You Linjun, Wang Zhanbo, Sun Yuanyuan, Jiang Jingwei, Yang Yong, Zhang Dayong, Tang Xinying
Аннотация
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.