Liu Wen-Ya, Yao Chuan-Sheng, Li Yue-Wen, Gao Xiang, Guo Li-Shuang, An Lin-Kun
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; State Key Laboratory of Anti-Infective Drug Discovery and Development, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China; Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou 510006, China.
Bioorg Med Chem. 2025 Jun 1;123:118161. doi: 10.1016/j.bmc.2025.118161. Epub 2025 Mar 19.
To find novel radiosensitizers, a series of phenanthridinone and phenanthridine derivatives were designed and synthesized based on the structural simplification strategy from the natural product oxynitidine scaffold. Colony formation assays indicated that the phenanthridine derivative B9 showed strong radiosensitizing activity in colorectal cancer HCT116 cells in a concentration- and dose-dependent manner. Further investigations revealed that B9 could increase intracellular ionizing radiation-induced ROS levels and DNA damage, and induce cancer cell apoptosis and cycle arrest at G2/M phase. These results suggest that phenanthridine chemotype is a novel scaffold for the discovery of radiosensitizers.
为了寻找新型放射增敏剂，基于天然产物氧化苦参碱骨架的结构简化策略，设计并合成了一系列菲啶酮和菲啶衍生物。集落形成试验表明，菲啶衍生物B9在结直肠癌HCT116细胞中表现出浓度和剂量依赖性的强放射增敏活性。进一步研究发现，B9可增加细胞内电离辐射诱导的ROS水平和DNA损伤，并诱导癌细胞凋亡和细胞周期阻滞于G2/M期。这些结果表明，菲啶化学类型是发现放射增敏剂的新型骨架。
