Synthesis and biological evaluation of novel PDMP analogues

Bioorg Med Chem. 2006 Aug 1;14(15):5273-84. doi: 10.1016/j.bmc.2006.03.048. Epub 2006 Apr 18.

Abstract

A new series of hybrid PDMP analogues, based both on PDMP and styryl analogues of natural ceramide, has been synthesized from D-serine. The synthetic route was developed such that future introduction of different aryl groups is straightforward. Biological evaluation, both in vitro on rat liver Golgi fractions as well as in HEK-293 and COS-7 cells, revealed two lead compounds with comparable inhibitory potency as PDMP, which could be elaborated to more potent inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • COS Cells
  • Cell Line
  • Cell Proliferation / drug effects
  • Chlorocebus aethiops
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Glucosyltransferases / antagonists & inhibitors*
  • Golgi Apparatus / drug effects*
  • Golgi Apparatus / enzymology
  • Humans
  • Liver / drug effects
  • Liver / enzymology
  • Molecular Structure
  • Morpholines / chemistry
  • Morpholines / pharmacology*
  • Rats
  • Structure-Activity Relationship
  • Subcellular Fractions / enzymology

Substances

  • Enzyme Inhibitors
  • Morpholines
  • RV 538
  • Glucosyltransferases
  • ceramide glucosyltransferase