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.

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