Synthesis of ferroquine enantiomers: first investigation of effects of metallocenic chirality upon antimalarial activity and cytotoxicity

Chembiochem. 2002 May 3;3(5):418-23. doi: 10.1002/1439-7633(20020503)3:5<418::AID-CBIC418>3.0.CO;2-P.

Abstract

Ferroquine (FQ) is a new antimalarial agent with a high blood schizotoncidal activity. Previous studies on this compound were done with racemate mixtures. As FQ possesses planar chirality, pure enantiomers were obtained by enzymatic resolution in order to compare their antimalarial activities and cytotoxicities. (+)-FQ and (-)-FQ were equally active in vitro, at nanomolar concentrations. Both enantiomers were slightly less active than the racemate in vivo; cytotoxicities were similar. Actually, the racemate represents the optimal formulation. To the best of our knowledge, this is the first investigation of biological activities of compounds with metallocenic chirality.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / pharmacology*
  • Antimalarials / toxicity
  • Cell Division / drug effects
  • Chloroquine / analogs & derivatives*
  • Chloroquine / chemical synthesis
  • Chloroquine / pharmacology*
  • Chloroquine / toxicity
  • Female
  • Ferric Compounds / chemical synthesis
  • Ferric Compounds / pharmacology*
  • Ferric Compounds / toxicity
  • In Vitro Techniques
  • Malaria / drug therapy
  • Mice
  • Plasmodium falciparum / drug effects*
  • Stereoisomerism
  • Tumor Cells, Cultured / drug effects

Substances

  • 7-chloro-4-((2-(N,N-dimethylaminomethyl))-N-methylferrocenylamino)quinoline
  • Antimalarials
  • Ferric Compounds
  • Chloroquine