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. Epub 2018 Feb 16.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alstonia / chemistry*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Glioma / drug therapy*
  • Glioma / pathology
  • Humans
  • Indoles / chemistry
  • Indoles / isolation & purification
  • Indoles / pharmacology*
  • Molecular Structure
  • Neoplastic Stem Cells / drug effects*
  • Plant Leaves / chemistry
  • Structure-Activity Relationship
  • Sugars / chemistry*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Indoles
  • Sugars