Semisynthesis of triptolide analogues: effect of B-ring substituents on cytotoxic activities

Bioorg Med Chem Lett. 2014 Dec 15;24(24):5671-5674. doi: 10.1016/j.bmcl.2014.10.069. Epub 2014 Oct 29.

Abstract

A series of B-ring modified analogues of triptolide were synthesized and tested for their cytotoxicity against two human tumor cell lines (U251 and PC-3). From the current investigation, the structure-cytotoxic activity relationships of these analogues suggested that the introduction of hydroxyl, epoxide, halogen or olefinic groups on C5 and/or C6 could still retain the cytotoxicity, albeit a little less potency, and the C7,C8-β-epoxide group of triptolide was essential to its potent cytotoxic activity.

Keywords: Cytotoxic; Diterpenoid; Structure–cytotoxic activity relationships; Synthesis; Triptolide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects*
  • Diterpenes / chemistry*
  • Diterpenes / pharmacology
  • Drug Screening Assays, Antitumor
  • Epoxy Compounds / chemistry
  • Epoxy Compounds / pharmacology
  • Glioma / drug therapy*
  • Humans
  • Male
  • Models, Molecular
  • Molecular Structure
  • Organic Chemicals
  • Phenanthrenes / chemistry*
  • Phenanthrenes / pharmacology
  • Prostatic Neoplasms / drug therapy*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Diterpenes
  • Epoxy Compounds
  • Organic Chemicals
  • Phenanthrenes
  • triptolide