Four Alkaloids from Alstonia scholaris with Antitumor Activity via Disturbing Glutathione Homeostasis

J Org Chem. 2025 Jan 24;90(3):1280-1287. doi: 10.1021/acs.joc.4c02450. Epub 2025 Jan 9.

Abstract

Alstoschoquinolines A-D (1-4) representing three unprecedented scaffolds were isolated from the leaves of Alstonia scholaris through direct separation by LC/MS detection. 1 and 2 consisted of a 5/6/5-coupled quinoline architecture containing six consecutive chiral carbons, while 3 and 4 possessed a bridged ring featuring 6/6/6/6 and 6/6/8/6 skeletons, respectively. They might be derived from the corynantheine-type indole alkaloid via sequential oxidation and rearrangement. Compound 3 exhibited a significant inhibitory effect on colon carcinoma cells by disturbing glutathione circulation.

MeSH terms

  • Alkaloids* / chemistry
  • Alkaloids* / isolation & purification
  • Alkaloids* / pharmacology
  • Alstonia* / chemistry
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Glutathione* / chemistry
  • Glutathione* / metabolism
  • Homeostasis / drug effects
  • Humans
  • Molecular Structure
  • Plant Leaves / chemistry
  • Quinolines / chemistry
  • Quinolines / isolation & purification
  • Quinolines / pharmacology

Substances

  • Glutathione
  • Alkaloids
  • Antineoplastic Agents, Phytogenic
  • Quinolines
  • Antineoplastic Agents