From a cytotoxic agent to the discovery of a novel antimalarial agent

Bioorg Med Chem Lett. 2013 Jan 15;23(2):584-7. doi: 10.1016/j.bmcl.2012.10.126. Epub 2012 Nov 15.

Abstract

A novel cytotoxin 3,5-bis(4-chlorobenzylidene)-1-[4-{2-(4-morpholinyl)ethoxy}phenyl-carbonyl]-4-piperidone hydrochloride 2 demonstrated potent antimalarial properties with IC(50) values of 0.60 and 1.97 μM against the drug sensitive D6 strain and the C235 drug-resistant strain of Plasmodium falciparum. This compound concentrates in red blood cells, lowers glutathione concentrations in erythrocytes and permeates across CACO-2 cells. These data reveal 2 to be a promising lead compound in the quest for novel antimalarial agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis*
  • Antimalarials / chemistry
  • Antimalarials / pharmacology
  • Caco-2 Cells
  • Drug Discovery*
  • Drug Resistance
  • Humans
  • Inhibitory Concentration 50
  • Morpholines / chemical synthesis*
  • Morpholines / chemistry
  • Morpholines / pharmacology
  • Piperidones / chemical synthesis*
  • Piperidones / chemistry
  • Piperidones / pharmacology
  • Plasmodium falciparum / drug effects

Substances

  • 3,5-bis(4-chlorobenzylidene)-1-(4-(2-(4-morpholinyl)ethoxy)phenyl-carbonyl)-4-piperidone
  • Antimalarials
  • Morpholines
  • Piperidones