Mechanism of action of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against Trypanosoma cruzi, the causative agent of Chagas' disease

Antimicrob Agents Chemother. 2003 Jun;47(6):2047-50. doi: 10.1128/AAC.47.6.2047-2050.2003.

Abstract

We investigated the molecular basis of the activity of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against Trypanosoma cruzi, the etiological agent of Chagas' disease. We found that growth inhibition of T. cruzi epimastigotes induced by this compound was associated with a reduction in the content of the parasite's endogenous sterols due to a specific blockade of their de novo synthesis at the level of squalene synthase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / metabolism
  • Animals
  • Dose-Response Relationship, Drug
  • Ergosterol / metabolism
  • Farnesyl-Diphosphate Farnesyltransferase / metabolism
  • Geranyltranstransferase
  • Humans
  • Microbial Sensitivity Tests
  • Phenyl Ethers / pharmacology*
  • Thiocyanates / pharmacology*
  • Trypanocidal Agents / pharmacology*
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / enzymology
  • Trypanosoma cruzi / growth & development
  • Trypanosoma cruzi / metabolism

Substances

  • 4-phenoxyphenoxyethyl thiocyanate
  • Phenyl Ethers
  • Thiocyanates
  • Trypanocidal Agents
  • Alkyl and Aryl Transferases
  • Geranyltranstransferase
  • Farnesyl-Diphosphate Farnesyltransferase
  • Ergosterol