Novel squaramides with in vitro liver stage antiplasmodial activity

Bioorg Med Chem. 2016 Apr 15;24(8):1786-92. doi: 10.1016/j.bmc.2016.03.005. Epub 2016 Mar 3.

Abstract

A structure-activity relationship study was performed with ten 8-aminoquinoline-squaramides compounds active against liver stage malaria parasites, using human hepatoma cells (Huh7) infected by Plasmodium berghei parasites. In addition, their blood-schizontocidal activity was assessed against chloroquine-resistant W2 strain Plasmodium falciparum. Compound 3 was 7.3-fold more potent than the positive control primaquine against liver-stage parasites, illustrating the importance of the squarate moiety to activity.

Keywords: 8-Aminoquinoline; Antiplasmodial activity; Liver stage; Malaria; Squaramide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / chemistry
  • Antiprotozoal Agents / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • HEK293 Cells
  • Humans
  • Liver / parasitology*
  • Malaria / drug therapy
  • Malaria / parasitology*
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Quinine / analogs & derivatives*
  • Quinine / chemical synthesis
  • Quinine / chemistry
  • Quinine / pharmacology
  • Structure-Activity Relationship

Substances

  • Antiprotozoal Agents
  • squaramide
  • Quinine