Dibenzylideneacetone analogues as novel Plasmodium falciparum inhibitors

Bioorg Med Chem Lett. 2011 May 15;21(10):3034-6. doi: 10.1016/j.bmcl.2011.03.037. Epub 2011 Apr 12.

Abstract

A series of dibenzylideneacetones (A1-A12) and some of their pyrazolines (B1-B4) were synthesized and evaluated in vitro for blood stage antiplasmodial properties in Plasmodium falciparum culture using SYBR-green-I fluorescence assay. The compound (1E, 4E)-1,5-bis(3,4-dimethoxyphenyl)penta-1,4-dien-3-one (A9) was found to be the most active with IC(50) of 1.97 μM against chloroquine-sensitive strain (3D7) and 1.69 μM against chloroquine-resistant field isolate (RKL9). The MTT based cytotoxicity assay on HeLa cell line has confirmed that A9 is selective in its action against malaria parasite (with a therapeutic index of 166). Our results revealed that these compounds exhibited promising antiplasmodial activities which can be further explored as potential leads for the development of cheaper, safe, effective and potent drugs against chloroquine-resistant malarial parasites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetone / chemistry*
  • Acetone / pharmacology
  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry*
  • Antimalarials / pharmacology*
  • Benzylidene Compounds / chemical synthesis
  • Benzylidene Compounds / chemistry*
  • Benzylidene Compounds / pharmacology
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Molecular Structure
  • Plasmodium falciparum / drug effects*
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology

Substances

  • Antimalarials
  • Benzylidene Compounds
  • Pyrazoles
  • Acetone