22-Oxocholestane oximes as potential anti-inflammatory drug candidates

22-Oxocholestanes bearing the oxime functionality in the side chain have been synthesized from diosgenin and evaluated in vivo as anti-inflammatory agents in an acute inflammation mouse ear model, against the commercial glucocorticoid dexamethasone. The final compounds were all regioselectively obta...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2019-04, Vol.168, p.78-86
Main Authors: Zeferino-Díaz, Reyna, Olivera-Castillo, Leticia, Dávalos, Alberto, Grant, George, Kantún-Moreno, Nuvia, Rodriguez-Canul, Rossanna, Bernès, Sylvain, Sandoval-Ramírez, Jesús, Fernández-Herrera, María A.
Format: Article
Language:English
Subjects:
22-Oxocholestanes
Expression of proinflammatory genes
Hydroxyimino steroids
Mouse ear inflammation model
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Summary:22-Oxocholestanes bearing the oxime functionality in the side chain have been synthesized from diosgenin and evaluated in vivo as anti-inflammatory agents in an acute inflammation mouse ear model, against the commercial glucocorticoid dexamethasone. The final compounds were all regioselectively obtained with an E configuration at the oxime double bond. The title compounds reduced ear-induced inflammation and edema. The most active oximes repressed the expression of proinflammatory genes TNF-α, COX-2, and IL-6; including macrophage migration inhibitory factor. Overall, our data suggest that 22-oxocholestane oximes exert a strong in vivo anti-inflammatory activity. [Display omitted] •22-oxocholestane oximes were synthesized from diosgenin.•Regioselectivity was found for E/Z but no for R/S configuration.•The new hydroxyimino steroids exert anti-inflammatory activity in vivo.•Oximes repressed the expression of proinflammatory genes (TNF-α, COX-2, IL-6).•The most active oximes downregulated MIF.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2019.02.035