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• W2013640088 abstract "ABSTRACT We describe the in vitro antiproliferative effects of the new triazole derivative UR-9825 against the protozoan parasite Trypanosoma ( Schizotrypanum ) cruzi , the causative agent of Chagas' disease in Latin America. The compound was found to be extremely active against the cultured (epimastigote) form of the parasite, equivalent to that present in the reduviid vector, with a MIC of 30 nM, a concentration 33-fold lower than that required with the reference compound ketoconazole. At that MIC, growth arrest coincided with depletion of the parasite's 4,14-desmethyl endogenous sterols (ergosterol, 24-ethylcholesta-5,7,22-trien-3b-ol, and precursors) and their replacement by methylated sterols (lanosterol, 24-methylenedihydrolanosterol, and obtusifoliol), as revealed by high-resolution gas chromatography coupled with mass spectrometry. This indicated that the primary mechanism of action of UR-9825 was inhibition of the parasite's sterol C14α demethylase, as seen with other azole derivatives. The phospholipid composition of growth-arrested epimastigotes was also altered, when compared to controls, with a significant increase in the content of phosphatidylethanolamine and phosphatidylserine and a concomitant reduction of the content of phosphatidylcholine. The clinically relevant intracellular amastigote form, grown in cultured Vero cells at 37°C, was even more sensitive to UR-9825, with a MIC of 10 nM, comparable to that for ketoconazole. The results showed that UR-9825 is among the most potent azole derivatives tested against this parasite and support in vivo studies with this compound." @default.
• W2013640088 created "2016-06-24" @default.
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• W2013640088 date "2000-09-01" @default.
• W2013640088 modified "2023-09-27" @default.
• W2013640088 title "In Vitro Antiproliferative Effects and Mechanism of Action of the New Triazole Derivative UR-9825 against the Protozoan Parasite <i>Trypanosoma</i> ( <i>Schizotrypanum</i> ) <i>cruzi</i>" @default.
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• W2013640088 doi "https://doi.org/10.1128/aac.44.9.2498-2502.2000" @default.
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