Design, synthesis and anticancer activity evaluation of novel C14 heterocycle substituted epi-triptolide

Eur J Med Chem. 2014 Feb 12:73:46-55. doi: 10.1016/j.ejmech.2013.11.044. Epub 2013 Dec 14.

Abstract

Two series of novel C14 heterocycle substituted epi-triptolide derivatives as potential anticancer agents were synthesized and tested for their cytotoxicity against SKOV-3 and PC-3 tumor cell lines. The introduction of C14β-aryl heterocycle aminomethyl substituent to the leading compound was found to be an effective modification method to retain the potent anticancer activity. Meanwhile, the series of epi-triptolide derivatives (21-40) with C14α-hydroxyl group, still retained the natural product's cytotoxicity. This is apparently challenges the classical structure-activity relationship of triptolide that considers the C14β-hydroxyl group to be essential for its anticancer activity.

Keywords: Anticancer; Heterocycle; PC-3; SKOV-3; Synthesis; Triptolide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Culture Techniques
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Diterpenes / chemical synthesis*
  • Diterpenes / chemistry
  • Diterpenes / pharmacology
  • Drug Design*
  • Epoxy Compounds / chemical synthesis
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology
  • Heterocyclic Compounds / chemistry*
  • Humans
  • Molecular Structure
  • Phenanthrenes / chemical synthesis*
  • Phenanthrenes / chemistry
  • Phenanthrenes / pharmacology
  • Stereoisomerism

Substances

  • Antineoplastic Agents
  • Diterpenes
  • Epoxy Compounds
  • Heterocyclic Compounds
  • Phenanthrenes
  • triptolide