Synthetic Modification of 9α- and 9β-Hydroxyparthenolide by Heck or Acylation Reactions and Evaluation of Cytotoxic Activities

Planta Med. 2017 May;83(7):661-671. doi: 10.1055/s-0042-119864. Epub 2016 Dec 5.

Abstract

Motivated by the widely reported anticancer activity of parthenolides and their derivatives, a series of new substituted parthenolides was efficiently synthesized. Structural modifications were performed at the C-9 and C-13 positions of 9α- and 9β-hydroxyparthenolide, which were isolated from the aerial parts of Anvillea radiata. Twenty-one derivatives were synthesized and evaluated for their in vitro cytotoxic activity against HS-683, SK-MEL-28, A549, and MCF-7 human cancer cell lines using the MTT colorimetric assay. Among the derivatives, seven exhibited excellent activity compared to 5-fluorouracil and etoposide against the four cell lines tested, with IC50 values ranging from 1.1 to 9.4 µM.

MeSH terms

  • Acylation
  • Antineoplastic Agents, Phytogenic / chemistry*
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Asteraceae / chemistry*
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Plant Extracts / chemistry*
  • Plant Extracts / pharmacology
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / pharmacology
  • Structure-Activity Relationship

Substances

  • 9-hydroxyparthenolide
  • Antineoplastic Agents, Phytogenic
  • Plant Extracts
  • Sesquiterpenes