A disubstituted NAD+ analogue is a nanomolar inhibitor of trypanosomal glyceraldehyde-3-phosphate dehydrogenase

Bioorg Med Chem Lett. 2001 Jan 22;11(2):95-8. doi: 10.1016/s0960-894x(00)00608-9.

Abstract

N6-Naphthalenemethyl-2'-methoxybenzamido-beta-NAD+, a derivative of a low micromolar first-generation inhibitor of trypanosomal glyceraldehyde phosphate dehydrogenase (GAPDH), was synthesized, taking advantage of methodology for the selective phosphitylation of nucleosides. The compound was found to be a poor alternate cosubstrate for GAPDH, but an extremely potent inhibitor. Although intended for use in crystallization trials, the analogue presents possibilities for further drug design.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Antiprotozoal Agents / chemical synthesis*
  • Antiprotozoal Agents / pharmacology
  • Cell Culture Techniques
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / pharmacology
  • Glyceraldehyde-3-Phosphate Dehydrogenases / antagonists & inhibitors*
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Muscle, Skeletal / cytology
  • NAD / analogs & derivatives*
  • NAD / chemical synthesis
  • NAD / pharmacology*
  • Rabbits
  • Structure-Activity Relationship
  • Trypanosoma / drug effects*
  • Trypanosoma / enzymology

Substances

  • Antiprotozoal Agents
  • Enzyme Inhibitors
  • NAD
  • Glyceraldehyde-3-Phosphate Dehydrogenases