Discovery of novel inhibitors targeting enoyl-acyl carrier protein reductase in Plasmodium falciparum by structure-based virtual screening

Biochem Biophys Res Commun. 2007 Jul 6;358(3):686-91. doi: 10.1016/j.bbrc.2007.04.113. Epub 2007 Apr 26.

Abstract

There is a dire need for novel therapeutics to treat the virulent malarial parasite, Plasmodium falciparum. Recently, the X-ray crystal structure of enoyl-acyl carrier protein reductase (ENR) in complex with triclosan has been determined and provides an opportunity for the rational design of novel inhibitors targeting the active site of ENR. Here, we report the discovery of several compounds by virtual screening and their experimental validation as high potency PfENR inhibitors.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Binding Sites
  • Caco-2 Cells
  • Crystallography, X-Ray
  • Drug Design*
  • Drug Evaluation, Preclinical
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors*
  • Humans
  • Hydrogen Bonding
  • Kinetics
  • Malaria / drug therapy
  • Models, Molecular
  • Plasmodium falciparum / enzymology*
  • Triclosan / chemistry
  • Triclosan / pharmacology

Substances

  • Antimalarials
  • Triclosan
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)