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
  • 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: [email protected].
  • 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: [email protected].
  • 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: [email protected].
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.