Synthesis, β-hematin inhibition studies and antimalarial evaluation of dehydroxy isotebuquine derivatives against Plasmodium berghei

Bioorg Med Chem. 2015 Aug 1;23(15):4755-4762. doi: 10.1016/j.bmc.2015.05.040. Epub 2015 May 31.

Abstract

Diverse dehydroxy-isotebuquine derivatives were prepared by using a five step synthetic sequence in good yields. All these new 4-aminoquinolines were evaluated as inhibitors of haemozoin formation, where most of them showed a significant inhibition value (% IHF >97). The best inhibitors were tested in vivo as potential antimalarials in mice infected with Plasmodium berghei ANKA chloroquine susceptible strain, three of them (11b, 11d and 11h) displayed an antimalarial activity comparable to that of chloroquine.

Keywords: 4-Aminoquinoline; Antimalarial activity; Haemozoin formation; Isotebuquine; Malaria; β-Hematin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / chemistry*
  • Aminoquinolines / pharmacology
  • Aminoquinolines / therapeutic use
  • Animals
  • Antimalarials / chemical synthesis*
  • Antimalarials / pharmacology
  • Antimalarials / therapeutic use
  • Chloroquine / pharmacology
  • Drug Evaluation, Preclinical
  • Hemeproteins / antagonists & inhibitors*
  • Hemeproteins / metabolism
  • Malaria / drug therapy
  • Malaria / pathology
  • Malaria / veterinary
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Plasmodium berghei / drug effects
  • Structure-Activity Relationship

Substances

  • Aminoquinolines
  • Antimalarials
  • Hemeproteins
  • hemozoin
  • tebuquine
  • Chloroquine