Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides

Bioorg Med Chem Lett. 2013 Jun 15;23(12):3551-5. doi: 10.1016/j.bmcl.2013.04.035. Epub 2013 Apr 24.

Abstract

The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding site of triclosan, a potent ENR inhibitor, is occluded from the solvent making the attachment of these linkers challenging. Herein, we have produced 3 new triclosan analogs with bulky A- and B-ring motifs, which protrude into the solvent allowing for the future attachment of molecular transporters for delivery.

Publication types

  • Letter
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Carrier Proteins / chemistry*
  • Carrier Proteins / metabolism
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / antagonists & inhibitors
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / chemistry*
  • Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / metabolism
  • Models, Molecular
  • Plasmodium falciparum / metabolism
  • Toxoplasma / metabolism
  • Triclosan / analogs & derivatives*
  • Triclosan / chemical synthesis
  • Triclosan / chemistry
  • Triclosan / pharmacology

Substances

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