Design, synthesis and evaluation of new tricyclic endoperoxides as potential antiplasmodial agents

Org Biomol Chem. 2014 Jul 28;12(28):5212-21. doi: 10.1039/c4ob00787e.

Abstract

Diastereoselective autoxidation allowed preparation of new tricyclic endoperoxides. These compounds and their methylated analogs were evaluated against the in vitro growth of Plasmodium falciparum, the malaria-causing parasite, showing moderate activities. However, hybrid molecules composed of the tricyclic peroxide moiety and 7-chloro-4-aminoquinoline were synthesized and displayed a marked increase in antiplasmodial activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemistry*
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology
  • Artemisinins / pharmacology
  • Chloroquine / pharmacology
  • Drug Design
  • Erythrocytes / drug effects
  • Erythrocytes / parasitology
  • Erythrocytes / pathology
  • Free Radicals / chemistry*
  • Humans
  • Hypoxanthine / metabolism
  • Inhibitory Concentration 50
  • Iron / chemistry*
  • Oxidation-Reduction
  • Peroxides / chemical synthesis*
  • Peroxides / pharmacology
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / growth & development
  • Tritium

Substances

  • Aminoquinolines
  • Antimalarials
  • Artemisinins
  • Free Radicals
  • Peroxides
  • Tritium
  • 7-chloro-4-aminoquinoline
  • Hypoxanthine
  • Chloroquine
  • artemisinin
  • Iron