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 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.