Probing the role of the covalent linkage of ferrocene into a chloroquine template

J Med Chem. 2006 Jul 27;49(15):4707-14. doi: 10.1021/jm060259d.

Abstract

A new therapeutic approach to malaria led to the discovery of ferroquine (FQ, SR97276). To assess the importance of the linkage of the ferrocenyl group to a 4-aminoquinoline scaffold, two series of 4-aminoquinolines, structurally related to FQ, were synthesized. Evaluation of antimalarial activity, physicochemical parameters, and the beta-hematin inhibition property indicate that the ferrocene moiety has to be covalently flanked by a 4-aminoquinoline and an alkylamine. Current data reinforced our choice of FQ as a drug candidate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines
  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Chloroquine / chemistry*
  • Ferrous Compounds / chemical synthesis*
  • Ferrous Compounds / chemistry
  • Ferrous Compounds / pharmacology
  • Hemeproteins / antagonists & inhibitors
  • Hemeproteins / chemical synthesis
  • Metallocenes
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects
  • Quinolines / chemical synthesis*
  • Quinolines / chemistry
  • Quinolines / pharmacology
  • Structure-Activity Relationship

Substances

  • Aminoquinolines
  • Antimalarials
  • Ferrous Compounds
  • Hemeproteins
  • Metallocenes
  • Quinolines
  • hemozoin
  • Chloroquine
  • ferroquine