Unprecedented sugar bridged bisindoles selective inhibiting glioma stem cells

Publication date: Available online 16 February 2018
Source:Bioorganic & Medicinal Chemistry
Author(s): Xin Wei, Zhi Dai, Jing Yang, Afsar Khan, Hao-Fei Yu, Yun-Li Zhao, Yi-Fen Wang, Ya-Ping Liu, Zi-Feng Yang, Wan-Yi Huang, Xin-Hua Wang, Xu-Dong Zhao, Xiao-Dong Luo
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 scafford. 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.

Graphical abstract

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