前所未有的糖桥双吲哚选择性抑制神经胶质瘤干细胞。
Unprecedented sugar bridged bisindoles selective inhibiting glioma stem cells.
机构信息
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, People's Republic of China; University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.
出版信息
Bioorg Med Chem. 2018 May 1;26(8):1776-1783. doi: 10.1016/j.bmc.2018.02.024. Epub 2018 Feb 16.
Unlike reported bisindoles linked by single bond directly, alstoniasidines A (1) and B (2), from Alstonia scholaris featuring unprecedented skeleton with two indole moieties bridged by a sugar, represented a novel bisindole type having strictosamide-glucopyranose-picraline scaffold. Both compounds exhibited selective cytotoxicity against human glioma stem cells (GSCs) and induced caspase-3 dependent extrinsic apoptosis by increasing the expression of interleukin 1 (IL-1), tumor necrosis factor (TNF-α), and the cleaved caspase-3, while damaged the unlimited proliferation and self-renewal capacity of GSCs. This finding might provide new type of leads for the selective killing of human glioma stem cells.
不同于报道的通过单键直接连接的双吲哚类化合物，来源于使君子科使君子属植物的冬凌草甲素（1）和冬凌草乙素（2）具有前所未有的骨架，其中两个吲哚部分通过糖桥连接，代表了一种新型的双吲哚类化合物，具有严格斯酰胺-吡喃葡萄糖- picraline 支架。这两种化合物对人神经胶质瘤干细胞（GSCs）表现出选择性细胞毒性，并通过增加白细胞介素 1（IL-1）、肿瘤坏死因子（TNF-α）和裂解的 caspase-3 的表达，诱导 caspase-3 依赖性细胞外凋亡，同时破坏 GSCs 的无限增殖和自我更新能力。这一发现可能为选择性杀伤人神经胶质瘤干细胞提供了新的类型的先导化合物。
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