Synthetic ferrocenic mefloquine and quinine analoguesas potential antimalarial agents

Eur J Med Chem. 2000 Jul-Aug;35(7-8):707-14. doi: 10.1016/s0223-5234(00)00178-1.

Abstract

A few years ago we proposed a strategy for the synthesis of new ferrocene-chloroquine analogues replacing the carbon chain of chloroquine by hydrophobic ferrocenyl moieties. Now, this strategy has been applied to the antimalarial amino-alcohols class to afford new potentially active analogues of mefloquine and quinine bearing a substituted ferrocenic group. The pathway used for the synthesis of the mefloquine analogues includes the coupling of an aminomethyl substituted ferrocene carboxaldehyde with a lithio quinoline compound. On the other hand, the synthesis of quinine analogues was ensured by the 'inverse' reaction of a lithio aminomethyl ferrocene with a quinoline carboxaldehyde. The configurations of each diastereoisomer were unambiguously determined by spectroscopic data. The mechanistic interpretations were fully discussed. Ferrocenyl analogues of mefloquine and quinine exhibited a lower antimalarial activity than mefloquine and quinine themselves. Comparing optical isomers, those isomers dissimilar to ferrocenyl derivatives presented better antimalarial activities than those similar to ferrocenyl.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimalarials / chemical synthesis
  • Antimalarials / pharmacology*
  • Ferrous Compounds / chemistry*
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Mefloquine / analogs & derivatives*
  • Mefloquine / chemical synthesis
  • Mefloquine / pharmacology
  • Metallocenes
  • Plasmodium falciparum / drug effects
  • Quinine / analogs & derivatives*
  • Quinine / chemical synthesis
  • Quinine / pharmacology

Substances

  • Antimalarials
  • Ferrous Compounds
  • Metallocenes
  • Quinine
  • Mefloquine
  • ferrocene