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 principales: Veleiro, A.S., Pecci, A., Monteserín, M.C., Baggio, R., Garland, M.T., Lantos, C.P., Burton, G.
Formato: JOUR
Materias:
19 sulfanylpregn 5 ene
21 hydroxy 6,19 epithioprogesterone
21 hydroxy 6,19 epithioprogesterone s,s dioxide
6,19 epithioprogesterone
dexamethasone
fluorescein isothiocyanate
immunoglobulin enhancer binding protein
lipocortin 5
progesterone derivative
sulfur derivative
tumor necrosis factor alpha
unclassified drug
animal cell
antiimmunosuppressive activity
apoptosis
article
controlled study
cyclization
drug activity
drug structure
drug synthesis
enzyme inhibition
HeLa cell
human
human cell
iodination
nonhuman
parameter
rat
structure analysis
thymocyte
Animals
Apoptosis
Cercopithecus aethiops
COS Cells
Desoxycorticosterone
Dexamethasone
Glucocorticoids
Hela Cells
Humans
Immune Tolerance
Male
Mice
Molecular Conformation
Molecular Structure
NF-kappa B
Progesterone
Rats
Rats, Sprague-Dawley
Receptors, Progesterone
Stereoisomerism
Structure-Activity Relationship
Sulfides
Thymus Gland
Tumor Necrosis Factor-alpha
Acceso en línea:http://hdl.handle.net/20.500.12110/paper_00222623_v48_n18_p5675_Veleiro
Aporte de:
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires
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.

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