Antimalarial Effect of 3-Methoxy-1,2-Dioxetanes on the Erythrocytic Cycle of Plasmodium falciparum

Chem Biol Drug Des. 2015 Dec;86(6):1373-7. doi: 10.1111/cbdd.12599. Epub 2015 Jun 20.

Abstract

The antimalarial activity of peroxides most likely originates from their interaction with iron(II) species located inside the malaria parasite, which forms destructive radical species through a Fenton-like mechanism. This article reports the first evaluation of the in vitro antimalarial activity of three peroxides of the class 1,2-dioxetanes against Plasmodium falciparum; the results reveal that the studied 3-methoxy-1,2-dioxetanes display significant antimalarial activity, at a similar level as artemisinin and also that their reactivity toward iron(II) correlate linearly with their antimalarial activity.

Keywords: 1,2-dioxetanes; Fenton reaction; Plasmodium falciparum; antimalarial peroxides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Artemisinins / pharmacology
  • Drug Design
  • Drug Evaluation, Preclinical
  • Erythrocytes / drug effects
  • Erythrocytes / parasitology
  • Hemolysis / drug effects
  • Humans
  • In Vitro Techniques
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology
  • Peroxides / chemistry*
  • Peroxides / pharmacology*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / growth & development
  • Plasmodium falciparum / pathogenicity

Substances

  • Antimalarials
  • Artemisinins
  • Peroxides
  • artemisinin