Mechanism of action of 4-phenoxyphenoxyethyl thiocyanate (WC-9) against Trypanosoma cruzi, the causative agent of Chagas' disease.
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.
Urbina
Julio A
JA
Laboratorio de Quimica Biológica, Centro de Bioquimica y Biofisica, Instituto Venezolano de Investigaciones Cientificas, Carretera Panamericana, Caracas 1020, Venezuela. jaurbina@ivic.ve
Concepcion
Juan Luis
JL
Montalvetti
Andrea
A
Rodriguez
Juan B
JB
Docampo
Roberto
R
D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004875:Ergosterol / Q000378:metabolism; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000378:metabolism; D051228:Geranyltranstransferase; D006801:Humans; D008826:Microbial Sensitivity Tests; D010647:Phenyl Ethers / Q000494:pharmacology*; D013861:Thiocyanates / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000201:enzymology / Q000254:growth & development / Q000378:metabolism
C111921:4-phenoxyphenoxyethyl thiocyanate; D010647:Phenyl Ethers; D013861:Thiocyanates; D014344:Trypanocidal Agents; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase; D013186:Farnesyl-Diphosphate Farnesyltransferase; D004875:Ergosterol