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Biomolecules ; 9(9)2019 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-31547423

RESUMO

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.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Ergosterol/análogos & derivados , Pleurotus/química , Trypanosoma cruzi/efeitos dos fármacos , Membrana Celular/efeitos dos fármacos , Membrana Celular/metabolismo , Cristalografia por Raios X , Sistema Enzimático do Citocromo P-450/química , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Ergosterol/química , Ergosterol/farmacologia , Modelos Moleculares , Simulação de Acoplamento Molecular , Estrutura Molecular , Trypanosoma cruzi/metabolismo
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