6,19-Sulfur-Bridged Progesterone Analogues with Antiimmunosuppressive Activity
2005; American Chemical Society; Volume: 48; Issue: 18 Linguagem: Inglês
10.1021/jm049266x
ISSN1520-4804
AutoresAdriana S. Veleiro, Adalı́ Pecci, María Monteserín, Ricardo Baggio, M.T. Garland, Carlos P. Lantos, Gerardo Burton,
Tópico(s)Genomics, phytochemicals, and oxidative stress
ResumoSulfur-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.
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