2. Academic Validation
  3. Unprecedented sugar bridged bisindoles selective inhibiting glioma stem cells

Unprecedented sugar bridged bisindoles selective inhibiting glioma stem cells

  • Bioorg Med Chem. 2018 May 1;26(8):1776-1783. doi: 10.1016/j.bmc.2018.02.024.
Xin Wei 1,  Zhi Dai 2,  Jing Yang 3,  Afsar Khan 4,  Hao-Fei Yu 1,  Yun-Li Zhao 3,  Yi-Fen Wang 3,  Ya-Ping Liu 3,  Zi-Feng Yang 5,  Wan-Yi Huang 5,  Xin-Hua Wang 6,  Xu-Dong Zhao 7,  Xiao-Dong Luo 8
Affiliations

Affiliations

  • 1 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.
  • 2 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.
  • 3 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.
  • 4 Department of Chemistry, COMSATS Institute of Information Technology, Abbottabad 22060, Pakistan.
  • 5 Guangzhou Medical University, Guangzhou 511436, People's Republic of China.
  • 6 Guangzhou Medical University, Guangzhou 511436, People's Republic of China. Electronic address: xinhuaw@gzhmu.edu.cn.
  • 7 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. Electronic address: zhaoxudong@mail.kiz.ac.cn.
  • 8 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; Guangzhou Medical University, Guangzhou 511436, People's Republic of China. Electronic address: xdluo@mail.kib.ac.cn.
PMID: 29486949 DOI: 10.1016/j.bmc.2018.02.024
Abstract

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.

Keywords

Alstonia scholaris; Alstoniasidines A and B; Glioma stem cells; Sugar bridged bisindole.

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