Targeted isolation of cytotoxic germacranolide sesquiterpenes from Elephantopus scaber L. using small molecule accurate recognition technology

Bioorg Chem. 2020 Nov:104:104314. doi: 10.1016/j.bioorg.2020.104314. Epub 2020 Sep 24.

Abstract

Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC50, 3.3-9.9 μM) and Hep3B (IC50, 4.5-8.6 μM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.

Keywords: Apoptosis; Cytotoxicity; Elephantopus scaber; Germacranolide sesquiterpenes; Small molecule accurate recognition technology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / chemistry
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Asteraceae / chemistry*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Plant Extracts / chemistry
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Sesquiterpenes, Germacrane / chemistry
  • Sesquiterpenes, Germacrane / isolation & purification
  • Sesquiterpenes, Germacrane / pharmacology*
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / isolation & purification
  • Small Molecule Libraries / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Sesquiterpenes, Germacrane
  • Small Molecule Libraries