Synthesis and evaluation of dihydroartemisinin and dihydroartemisitene acetal dimers showing anticancer and antiprotozoal activity

Bioorg Med Chem. 2009 Jan 15;17(2):741-51. doi: 10.1016/j.bmc.2008.11.050. Epub 2008 Nov 25.


Twelve artemisinin acetal dimers were synthesized and tested for antitumor activity in the National Cancer Institute (NCI) in vitro human tumor 60 cell line assay, producing a mean GI(50) concentration between 8.7 (least active) and 0.019 microM (most active). The significant activity of the compounds in this preliminary screen led to additional in vitro antitumor and antiangiogenesis studies. Several active dimers were also evaluated in the in vivo NCI hollow fiber assay followed by a preliminary xenograft study. The title compounds were found to be active against solid tumor-derived cell lines and showed good correlation with other artemisinin-based molecules in the NCI database. The dimers were also evaluated for their antimalarial and antileishmanial activities. The antimalarial activity ranged from 0.3 to 32 nM (IC(50)), compared to 9.9 nM for artemisinin.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Angiogenesis Inhibitors
  • Animals
  • Antimalarials
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / pharmacology
  • Artemisinins / chemical synthesis*
  • Artemisinins / pharmacology
  • Cell Line, Tumor
  • Dimerization
  • Drug Screening Assays, Antitumor
  • Humans
  • Leishmania / drug effects
  • Mice
  • Structure-Activity Relationship
  • Xenograft Model Antitumor Assays


  • Angiogenesis Inhibitors
  • Antimalarials
  • Antineoplastic Agents
  • Antiprotozoal Agents
  • Artemisinins