Antiplasmodial activities of 4-aminoquinoline-statine compounds

Bioorg Med Chem Lett. 2012 Sep 15;22(18):5915-8. doi: 10.1016/j.bmcl.2012.07.069. Epub 2012 Jul 27.

Abstract

We report the discovery of new potent inhibitors of the growth of Plasmodium falciparum chloroquine (CQ)-resistant W2 strain. These compounds were designed using the double drug approach by introducing a residue able to enhance the accumulation of plasmepsins inhibitors into the food vacuole. Some of the molecules were more active than CQ against CQ-resistant strain and showed good selectivity against cathepsin D.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Amino Acids / pharmacology*
  • Aminoquinolines / chemistry
  • Aminoquinolines / pharmacology*
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Cathepsin D / antagonists & inhibitors*
  • Cathepsin D / metabolism
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / growth & development
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Amino Acids
  • Aminoquinolines
  • Antimalarials
  • Protease Inhibitors
  • Cathepsin D
  • 4-aminoquinoline
  • statine