Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents

Bioorg Med Chem Lett. 2001 Jan 22;11(2):251-4. doi: 10.1016/s0960-894x(00)00643-0.

Abstract

Several N-(3-phenylpropyl)-substituted spermidine and spermine derivatives were prepared and found to be potent competitive inhibitors of Trypanosoma cruzi trypanothione reductase (seven compounds with Ki values < 5 microM are described). The most effective inhibitor studied was compound 12 with a Ki value of 0.151 microM. Six of the compounds described are also effective trypanocides with IC50 values < 1 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Combinatorial Chemistry Techniques
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Inhibitory Concentration 50
  • Kinetics
  • NADH, NADPH Oxidoreductases / antagonists & inhibitors*
  • Polyamines / chemical synthesis
  • Polyamines / chemistry
  • Polyamines / pharmacology*
  • Spermidine / analogs & derivatives
  • Spermine / analogs & derivatives
  • Structure-Activity Relationship
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanosoma brucei brucei / enzymology
  • Trypanosoma cruzi / enzymology

Substances

  • Enzyme Inhibitors
  • Polyamines
  • Trypanocidal Agents
  • Spermine
  • NADH, NADPH Oxidoreductases
  • trypanothione reductase
  • Spermidine