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.
Gang Liu  1 ,  Shanshan Song  2 ,  Shiqi Shu  3 ,  Zehong Miao  2 ,  Ao Zhang  1 ,  Chunyong Ding  4
Affiliations
  • 1. CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
  • 2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China.
  • 3. Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Gulou District, Nanjing 210009, China.
  • 4. CAS Key Laboratory of Receptor Research, and Synthetic Organic & Medicinal Chemistry Laboratory, Shanghai Institute of Materia Medica (SIMM), Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: [email protected].
PMID: 26318055 DOI: 10.1016/j.ejmech.2015.08.035
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.