The comparative antimalarial properties of weak base and neutral synthetic ozonides

Bioorg Med Chem Lett. 2010 Jan 15;20(2):563-6. doi: 10.1016/j.bmcl.2009.11.088. Epub 2009 Nov 22.

Abstract

Thirty-three N-acyl 1,2,4-dispiro trioxolanes (secondary ozonides) were synthesized. For these ozonides, weak base functional groups were not required for high antimalarial potency against Plasmodium falciparum in vitro, but were necessary for high antimalarial efficacy in Plasmodium berghei-infected mice. A wide range of LogP/D(pH)(7.4) values were tolerated, although more lipophilic ozonides tended to be less metabolically stable.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacokinetics
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / chemistry
  • Heterocyclic Compounds / pharmacokinetics
  • Mice
  • Plasmodium falciparum / drug effects
  • Rats

Substances

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