Ferroquine, an ingenious antimalarial drug: thoughts on the mechanism of action

Molecules. 2008 Nov 20;13(11):2900-7. doi: 10.3390/molecules13112900.

Abstract

Ferroquine (FQ or SR97193) is a novel antimalarial drug candidate, currently in development at Sanofi-Aventis. In contrast to conventional drugs, FQ is the first organometallic drug: a ferrocenyl group covalently flanked by a 4-aminoquinoline and a basic alkylamine. FQ is able to overcome the CQ resistance problem, an important limit to the control of Plasmodium falciparum, the principal causative agent of malaria. After fifteen years of effort, it is now possible to propose a multifactorial mechanism of action of FQ by its capacity to target lipids, to inhibit the formation of hemozoin and to generate reactive oxygen species.

MeSH terms

  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Animals
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Drug Resistance
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / pharmacology*
  • Hemin / antagonists & inhibitors
  • Lipids / chemistry
  • Metallocenes
  • Plasmodium falciparum / drug effects*
  • Reactive Oxygen Species / chemical synthesis

Substances

  • Aminoquinolines
  • Antimalarials
  • Ferrous Compounds
  • Lipids
  • Metallocenes
  • Reactive Oxygen Species
  • Hemin
  • ferroquine