1. 22-Oxocholestane oximes as potential anti-inflammatory drug candidates.
- Author
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Zeferino-Díaz R, Olivera-Castillo L, Dávalos A, Grant G, Kantún-Moreno N, Rodriguez-Canul R, Bernès S, Sandoval-Ramírez J, and Fernández-Herrera MA
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal chemical synthesis, Anti-Inflammatory Agents, Non-Steroidal chemistry, Cholestanes chemical synthesis, Cholestanes chemistry, Cyclooxygenase 2 genetics, Cyclooxygenase 2 metabolism, Disease Models, Animal, Dose-Response Relationship, Drug, Ear Diseases metabolism, Edema metabolism, Inflammation metabolism, Interleukin-6 genetics, Interleukin-6 metabolism, Macrophages drug effects, Macrophages metabolism, Male, Mice, Molecular Structure, Oximes chemical synthesis, Oximes chemistry, Structure-Activity Relationship, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cholestanes pharmacology, Ear Diseases drug therapy, Edema drug therapy, Inflammation drug therapy, Oximes pharmacology
- Abstract
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., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)
- Published
- 2019
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