Design and synthesis of molecular probes for the determination of the target of the anthelmintic drug praziquantel

Bioorg Med Chem Lett. 2014 Jun 1;24(11):2469-72. doi: 10.1016/j.bmcl.2014.04.014. Epub 2014 Apr 13.

Abstract

Schistosomiasis is a highly prevalent neglected tropical disease caused by blood-dwelling helminths of the genus Schistosoma. Praziquantel (PZQ) is the only drug available widely for the treatment of this disease and is administered in racemic form, even though only the (R)-isomer has significant anthelmintic activity. Progress towards the development of a second generation of anthelmintics is hampered by a lack of understanding of the mechanism of action of PZQ. In this Letter, we report an efficient protocol for the small-scale separation of enantiomers of 2 (hydrolyzed PZQ) using supercritical fluid chromatography (SFC). The enantiopure 2 was then used to develop several molecular probes, which can potentially be used to help identify the protein target of PZQ and study its mode of action.

Keywords: Anthelmintic; Molecular probes; Praziquantel; Schistosomiasis; Supercritical fluid chromatography (SFC).

Publication types

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

MeSH terms

  • Animals
  • Anthelmintics / chemical synthesis
  • Anthelmintics / chemistry
  • Anthelmintics / pharmacology*
  • Chromatography, Supercritical Fluid
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Male
  • Models, Molecular
  • Molecular Probes / chemical synthesis*
  • Molecular Probes / chemistry
  • Molecular Probes / pharmacology*
  • Molecular Structure
  • Molecular Targeted Therapy
  • Praziquantel / chemical synthesis
  • Praziquantel / chemistry
  • Praziquantel / pharmacology*
  • Schistosoma mansoni / drug effects*
  • Schistosoma mansoni / metabolism*
  • Schistosomiasis mansoni / drug therapy
  • Schistosomiasis mansoni / parasitology
  • Stereoisomerism
  • Substrate Specificity

Substances

  • Anthelmintics
  • Molecular Probes
  • Praziquantel