Novel spirobicyclic artemisinin analogues (artemalogues): Synthesis and antitumor activities

Eur J Med Chem. 2015 Oct 20:103:17-28. doi: 10.1016/j.ejmech.2015.08.035. Epub 2015 Aug 18.

Abstract

The sesquiterpene lactone framework of artemisinin was used as a drug repositioning prototype for the development of novel antitumor drugs. Several series of novel artemisinin analogues (artemalogues) were designed and synthesized through 1,3-dipolar cycloaddition of artemisitene with nitrile oxides or nitrones. The isoxazolidine-containing spirobicyclic artemalogue 11b turns out to be the most potent with low micromolar IC₅₀ values against all three tumor cells, which were at least 4- to 14-fold more potent than the parent artemisinin.

Keywords: 1,3-dipolar cycloaddition; Antiprolifereative effect; Artemisinin; Spirobicyclic artemalogues; Stereoconfiguration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Artemisinins / chemical synthesis
  • Artemisinins / chemistry
  • Artemisinins / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Spiro Compounds / chemical synthesis
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Artemisinins
  • Spiro Compounds
  • artemisinin