2024-03-29T09:03:39Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/871462020-10-05T13:28:00Zcom_10261_81com_10261_5col_10261_334
Porcal, Williams
Hernández, Paola
Boiani, Mariana
Aguirre, Gabriela
Boiani, Lucía
Chidichimo, Agustina
Cazzulo, Juan J.
Campillo, Nuria E.
Páez, Juan A.
Castro, Ana
Krauth-Siegel, R. Luise
Davies, Carolina
Basombrío, Miguel Ángel
González, Mercedes
Cerecetto, Hugo
2013-11-20T12:26:54Z
2013-11-20T12:26:54Z
2007
Journal of Medicinal Chemistry 50: 6004- 6015 (2007)
http://hdl.handle.net/10261/87146
10.1021/jm070604e
New benzofuroxans were developed and studied as antiproliferative Trypanosoma cruzi agents. Compounds displayed remarkable in vitro activities against different strains, Tulahuen 2, CL Brener and Y. Its unspecific cytotoxicity was evaluated using human macrophages being not toxic at a concentration at least 8 times, and until 250 times, that of its T. cruzi IC50. Some biochemical pathways were studied, namely parasite respiration, cysteinyl active site enzymes and reaction with glutathione, as target for the mechanism of action. Not only T. cruzi respiration but also Cruzipain or trypanothione reductase were not affected, however the most active derivatives, the vinylsulfinyl- and vinylsulfonyl-containing benzofuroxans, react with glutathione in a redox pathway. Furthermore, the compounds showed good in vivo activities when they were studied in an acute murine model of Chagas' disease. The compounds were able to reduce the parasite loads of animals with fully established T. cruzi infections. © 2007 American Chemical Society.
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In vivo anti-chagas vinylthio-, vinylsulfinyl-, and vinylsulfonylbenzofuroxan derivatives
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