Ozonide Antimalarial Activity in the Context of Artemisinin-Resistant Malaria

Trends Parasitol. 2019 Jul;35(7):529-543. doi: 10.1016/j.pt.2019.05.002. Epub 2019 Jun 5.


The ozonides are one of the most advanced drug classes in the antimalarial development pipeline and were designed to improve on limitations associated with current front-line artemisinin-based therapies. Like the artemisinins, the pharmacophoric peroxide bond of ozonides is essential for activity, and it appears that these antimalarials share a similar mode of action, raising the possibility of cross-resistance. Resistance to artemisinins is associated with Plasmodium falciparum mutations that allow resistant parasites to escape short-term artemisinin-mediated damage (elimination half-life ~1 h). Importantly, some ozonides (e.g., OZ439) have a sustained in vivo drug exposure profile, providing a major pharmacokinetic advantage over the artemisinin derivatives. Here, we describe recent progress made towards understanding ozonide antimalarial activity and discuss ozonide utility within the context of artemisinin resistance.

Keywords: artemisinin resistance; artemisinins; mechanism of action; ozonide antimalarials.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Artemisinins / pharmacology*
  • Drug Resistance / drug effects*
  • Drug Resistance / genetics
  • Heterocyclic Compounds / pharmacology*
  • Heterocyclic Compounds / therapeutic use*
  • Humans
  • Malaria / drug therapy*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / genetics


  • 1,2,4-trioxane
  • Artemisinins
  • Heterocyclic Compounds