The interaction of artemisinin with malarial hemozoin

Mol Biochem Parasitol. 1994 Jan;63(1):121-8. doi: 10.1016/0166-6851(94)90014-0.

Abstract

[14C]Artemisinin was taken up by Plasmodium falciparum in culture and concentrated in hemozoin. In vitro, hemin and artemisinin were found to undergo a chemical reaction forming two major products which were isolated by high-performance liquid chromatography (HPLC). The m/z values of the two products were 856 and 871. Thin-layer chromatography (TLC) and HPLC of hemozoin isolated from [14C]artemisinin-treated parasites showed that the majority of the hemozoin-associated radioactivity comigrated with the synthetic adducts. When [14C]artemisinin was incubated with isolated hemozoin, [14C]artemisinin disappeared from the solution in a time-dependent manner. Some of the radioactivity present in the treated hemozoin also comigrated with the adducts on TLC. Thus, artemisinin appears to react covalently with heme in malaria hemozoin both in vitro and in situ.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / metabolism*
  • Antimalarials / pharmacokinetics
  • Antimalarials / pharmacology
  • Artemisinins*
  • Biological Transport, Active
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Drugs, Chinese Herbal / metabolism
  • Drugs, Chinese Herbal / pharmacokinetics
  • Drugs, Chinese Herbal / pharmacology
  • Hemeproteins / metabolism*
  • Humans
  • In Vitro Techniques
  • Malaria, Falciparum / drug therapy
  • Malaria, Falciparum / parasitology
  • Plasmodium falciparum / drug effects
  • Plasmodium falciparum / metabolism*
  • Sesquiterpenes / metabolism*
  • Sesquiterpenes / pharmacokinetics
  • Sesquiterpenes / pharmacology

Substances

  • Antimalarials
  • Artemisinins
  • Drugs, Chinese Herbal
  • Hemeproteins
  • Sesquiterpenes
  • hemozoin
  • artemisinine