2. Academic Validation
  3. In vivo anti-Chagas vinylthio-, vinylsulfinyl-, and vinylsulfonylbenzofuroxan derivatives

In vivo anti-Chagas vinylthio-, vinylsulfinyl-, and vinylsulfonylbenzofuroxan derivatives

  • J Med Chem. 2007 Nov 29;50(24):6004-15. doi: 10.1021/jm070604e.
Williams Porcal 1,  Paola Hernández,  Mariana Boiani,  Gabriela Aguirre,  Lucía Boiani,  Agustina Chidichimo,  Juan J Cazzulo,  Nuria E Campillo,  Juan A Paez,  Ana Castro,  R Luise Krauth-Siegel,  Carolina Davies,  Miguel Angel Basombrío,  Mercedes González,  Hugo Cerecetto
Affiliations

Affiliation

  • 1 Departamento de Química Orgánica, Facultad de Ciencias and Facultad de Química, Universidad de la República, Montevideo, Uruguay.
PMID: 17960923 DOI: 10.1021/jm070604e
Abstract

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.

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