In vivo anti-chagas vinylthio-, vinylsulfinyl-, and vinylsulfonylbenzofuroxan derivatives
| Autor: | Agustina Chidichimo, Mercedes González, Nuria E. Campillo, Juan José Cazzulo, Juan A. Páez, Hugo Cerecetto, Ana Castro, Gabriela Aguirre, Miguel Angel Basombrío, Paola Hernández, Mariana Boiani, Carolina Davies, Williams Porcal, Lucía Boiani, R Luise Krauth-Siegel |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Chagas disease
Models Molecular Vinyl Compounds Trypanosoma cruzi Protozoan Proteins Antibodies Protozoan Cruzipain Cell Line chemistry.chemical_compound Mice Structure-Activity Relationship Oxygen Consumption In vivo Drug Discovery parasitic diseases medicine Animals Humans Chagas Disease NADH NADPH Oxidoreductases Sulfones Cytotoxicity chemistry.chemical_classification Benzoxazoles biology Macrophages Stereoisomerism Glutathione medicine.disease biology.organism_classification Trypanocidal Agents Cysteine Endopeptidases Enzyme Biochemistry Mechanism of action chemistry Molecular Medicine Female medicine.symptom Oxidation-Reduction |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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