6,19-Sulfur-bridged progesterone analogues with antiimmunosuppressive activity

Sulfur-bridged pregnanes 6,19-epithioprogesterone, 21-hydroxy-6,19- epithioprogesterone, and the corresponding sulfoxides and sulfones were synthesized and tested as blockers of the immunosuppresive activity of dexamethasone in rat thymocytes. A new one-pot procedure is described for the preparation...

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Detalles Bibliográficos
Autores: Veleiro, Adriana Silvia, Pecci, Adali, Monteserín, María C., Baggio, Ricardo Fortunato, Garland, María T., Lantos, Carlos Pedro, Burton, Gerardo
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2005
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/98780
Acceso en línea:http://hdl.handle.net/11336/98780
Access Level:acceso abierto
Palabra clave:steroid analogs
https://purl.org/becyt/ford/3.5
https://purl.org/becyt/ford/3
Descripción
Sumario:Sulfur-bridged pregnanes 6,19-epithioprogesterone, 21-hydroxy-6,19- epithioprogesterone, and the corresponding sulfoxides and sulfones were synthesized and tested as blockers of the immunosuppresive activity of dexamethasone in rat thymocytes. A new one-pot procedure is described for the preparation of 6,19-epithioprogesterone and related compounds by iodocyclization of a 19-sulfanylpregn-5-ene. Antiimmunosuppresive activity was evaluated by the ability of the different steroids to block dexamethasone-mediated apoptosis in thymocytes and dexamethasone-mediated inhibition of the NFκ-B transcription factor activity. DNA fragmentation and annexin V-FITC positive cells were taken as parameters of apoptosis whereas NFκ-B activity was tested by the expression of the reporter vector κB-luciferase by TNF-α in Hela cells. 21-Hydroxy-6,19-epithioprogesterone S,S-dioxide had improved activity in both parameters, while 21-hydroxy-6,19-epithioprogesterone had improved activity only in blocking dexamethasone-induced programmed cell death. © 2005 American Chemical Society.