Optimising inhibitors of trypanothione reductase using solid-phase chemistry

Bioorg Med Chem Lett. 2000 Oct 16;10(20):2367-9. doi: 10.1016/s0960-894x(00)00471-6.

Abstract

A series of inhibitors of the enzyme trypanothione reductase has been identified using directed solid-phase chemistry. The compounds were based on a series of polyamine scaffolds and used the natural product kukoamine A as the lead structure. A compound with a Ki of 76 nM was identified, although somewhat surprisingly the compound appeared to be noncompetitive in nature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Glutathione Reductase / antagonists & inhibitors
  • Kinetics
  • Molecular Structure
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • Polyamines / chemical synthesis*
  • Polyamines / chemistry
  • Polyamines / pharmacology
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology

Substances

  • Enzyme Inhibitors
  • Polyamines
  • Trypanocidal Agents
  • NADH, NADPH Oxidoreductases
  • trypanothione reductase
  • Glutathione Reductase