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Biomolecules ; 9(9)2019 09 12.
Artículo en Inglés | MEDLINE | ID: mdl-31547423

RESUMEN

Trypanosoma cruzi, which causes Chagas disease, is a significant health threat in many countries and affects millions of people. Given the magnitude of this disease, a broader understanding of trypanocidal mechanisms is needed to prevent and treat infection. Natural endoperoxides, such as ergosterol peroxide, have been shown to be toxic to parasites without causing harm to human cells or tissues. Although prior studies have demonstrated the trypanocidal activity of ergosterol peroxide, the cellular and molecular mechanisms remain unknown. The results of this study indicate that a free-radical reaction occurs in T. cruzi following ergosterol peroxide exposure, leading to cell death. Using a combination of biochemical, microscopic and in silico experimental approaches, we have identified, for the first time, the cellular and molecular cytotoxic mechanism of an ergosterol peroxide obtained from Pleurotus ostreatus (Jacq) P. Kumm. f. sp. Florida.


Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Ergosterol/análogos & derivados , Pleurotus/química , Trypanosoma cruzi/efectos de los fármacos , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Cristalografía por Rayos X , Sistema Enzimático del Citocromo P-450/química , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Ergosterol/química , Ergosterol/farmacología , Modelos Moleculares , Simulación del Acoplamiento Molecular , Estructura Molecular , Trypanosoma cruzi/metabolismo
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