Publications & Reports

Ozonide Antimalarial Activity in the Context of Artemisinin-Resistant Malaria.

Giannangelo C, Fowkes FJI, Simpson JA, Charman SA, Creek DJ
Drug Delivery, Disposition, and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Victoria, Australia.

Abstract

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.

Link to publisher’s web site

Publication

  • Journal: Trends in Parasitology
  • Published: 05/06/2019
  • Volume: 35
  • Issue: 7
  • Pagination: 529-543

Author

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