Cell permeation of a Trypanosoma brucei aldolase inhibitor: evaluation of different enzyme-labile phosphate protecting groups

Bioorg Med Chem Lett. 2006 Jul 1;16(13):3440-3. doi: 10.1016/j.bmcl.2006.04.010. Epub 2006 Apr 24.

Abstract

A series of four prodrugs directed against Trypanosoma brucei aldolase bearing various transient enzyme-labile phosphate protecting groups was developed. Herein, we describe the synthesis and evaluation of cell permeation of these prodrugs. The oxymethyl derivative was the most efficient prodrug with a good recovering of the free drug (IC(50)=20 microM) and without any measurable cytotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldehyde-Lyases / antagonists & inhibitors*
  • Animals
  • Cell Membrane Permeability / drug effects*
  • Drug Delivery Systems
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • In Vitro Techniques
  • Organophosphates / chemical synthesis
  • Organophosphates / chemistry
  • Organophosphates / pharmacology*
  • Parasitic Sensitivity Tests
  • Prodrugs / chemical synthesis
  • Prodrugs / chemistry
  • Prodrugs / pharmacology*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Trypanosoma brucei brucei / cytology
  • Trypanosoma brucei brucei / drug effects
  • Trypanosoma brucei brucei / enzymology*

Substances

  • Enzyme Inhibitors
  • Organophosphates
  • Prodrugs
  • Aldehyde-Lyases