Polyamine metabolism: a potential therapeutic target in trypanosomes

Science. 1980 Oct 17;210(4467):332-4. doi: 10.1126/science.6775372.

Abstract

alpha-Difluoromethylornithine (RMI 71,782), a specific irreversible inhibitor of the first step in polyamine biosynthesis, that is, the formation of putrescine from ornithine by ornithine decarboxylase, cures mice infected with a virulent, rodent-passaged strain of Trypanosoma brucei brucei. This parasite is closely related to the trypanosomes that cause human sleeping sickness. The drug, which is remarkably nontoxic, was effective when administered in drinking water or by intubation. The ability of the compound to inhibit ornithine decarboxylase in vitro was demonstrated by the reduced amounts of putrescine synthesized from tritiated ornithine in Trypanosoma brucei suspensions. These observations direct attention to polyamine metabolism as a target for chemotherapy of parasitic diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Eflornithine
  • Mice
  • Ornithine / analogs & derivatives
  • Ornithine / metabolism
  • Ornithine / pharmacology
  • Ornithine Decarboxylase Inhibitors
  • Polyamines / metabolism*
  • Trypanocidal Agents*
  • Trypanosoma brucei brucei / drug effects
  • Trypanosoma brucei brucei / metabolism
  • Trypanosomiasis, African / drug therapy*

Substances

  • Ornithine Decarboxylase Inhibitors
  • Polyamines
  • Trypanocidal Agents
  • Ornithine
  • Eflornithine