Artemisinin (qinghaosu): the role of intracellular hemin in its mechanism of antimalarial action

Mol Biochem Parasitol. 1991 Dec;49(2):181-9. doi: 10.1016/0166-6851(91)90062-b.

Abstract

Artemisinin (qinghaosu), is a promising new antimalarial drug derived from an ancient Chinese herbal remedy. When [13-14C]artemisinin is added to cultures of Plasmodium falciparum, it is converted into a product with different solubility and chromatographic properties than the parent drug. Artemisinin reacts with hemin in aqueous solution to form an adduct with an apparent molecular weight of 914 which has identical chromatographic, solubility, and electrophoretic behavior to the parasite-derived product. The reaction between artemisinin and hemin, when carried out in the presence of red cell membranes, leads to the oxidation of protein thiols. Malarial parasites are rich in hemin; artemisinin's reactivity toward hemin may explain its selective toxicity to malarial parasites.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antimalarials / pharmacology*
  • Artemisinins*
  • Chromatography, High Pressure Liquid
  • Chromatography, Thin Layer
  • Electrophoresis, Polyacrylamide Gel
  • Hemin / metabolism*
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / metabolism
  • Sesquiterpenes / pharmacology*
  • Spectrum Analysis

Substances

  • Antimalarials
  • Artemisinins
  • Sesquiterpenes
  • Hemin
  • artemisinin