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
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkyl and Aryl Transferases / metabolism
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Animals
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Dose-Response Relationship, Drug
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Ergosterol / metabolism
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Farnesyl-Diphosphate Farnesyltransferase / metabolism
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Geranyltranstransferase
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Humans
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Microbial Sensitivity Tests
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Phenyl Ethers / pharmacology*
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Thiocyanates / pharmacology*
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Trypanocidal Agents / pharmacology*
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Trypanosoma cruzi / drug effects*
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Trypanosoma cruzi / enzymology
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Trypanosoma cruzi / growth & development
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Trypanosoma cruzi / metabolism
Substances
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4-phenoxyphenoxyethyl thiocyanate
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Phenyl Ethers
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Thiocyanates
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Trypanocidal Agents
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Alkyl and Aryl Transferases
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Geranyltranstransferase
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Farnesyl-Diphosphate Farnesyltransferase
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Ergosterol