Artículo
5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene
Gerpe, Alejandra; Alvarez, Guzmán; Benítez, Diego; Boiani, Lucía; Quiroga, Martín; Hernández, Paola; Sortino, Maximiliano Andrés
; Zacchino, Susana Alicia Stella; González, Mercedes; Cerecetto, Hugo
Fecha de publicación:
11/2009
Editorial:
Pergamon-Elsevier Science Ltd
Revista:
Bioorganic & Medicinal Chemistry
ISSN:
0968-0896
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Chagas disease represents a serious public health problem in South America. The first line of treatment is Nifurtimox and Benznidazole which generate toxic effects in treated patients. We have recently shown that a number of 5-nitrofuranes possess activity against Trypanosoma cruzi through oxidative stress and inhibition of parasite ergosterol biosynthesis, specifically at the level of squalene epoxidase. Here, we identify new 5-nitrofuranes and the thia-analogues with excellent effects on the viability of T. cruzi and adequate parasite/mammal selectivity indexes. Analysis of the free sterols from parasite incubated, during 120 h, with the compounds showed that some of them accumulated squalene suggesting the squalene epoxidase activity inhibition of the parasite. Nifurtimox was able to accumulate squalene only at lower incubation times. Due to this fact some derivatives were also tested as antifungal agents. Quantitative structure-activity relationship studies were also performed showing relevant features for further new derivatives design. Taken together, the results obtained in the present work point to a more general effect of 5-nitrofuranes and 5-nitrothiophenes in trypanosomatids, opening potential therapeutic possibilities of them for these infectious diseases.
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Articulos(CCT - ROSARIO)
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos de CTRO.CIENTIFICO TECNOL.CONICET - ROSARIO
Articulos(IMIBIO-SL)
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Articulos de INST. MULTIDICIPLINARIO DE INV. BIO. DE SAN LUIS
Citación
Gerpe, Alejandra; Alvarez, Guzmán; Benítez, Diego; Boiani, Lucía; Quiroga, Martín; et al.; 5-Nitrofuranes and 5-nitrothiophenes with anti-Trypanosoma cruzi activity and ability to accumulate squalene; Pergamon-Elsevier Science Ltd; Bioorganic & Medicinal Chemistry; 17; 21; 11-2009; 7500-7509
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