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.
Keywords:
22-Oxocholestanes; Expression of proinflammatory genes; Hydroxyimino steroids; Mouse ear inflammation model.
Copyright © 2019 Elsevier Masson SAS. All rights reserved.
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
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Anti-Inflammatory Agents, Non-Steroidal / chemistry
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cholestanes / chemical synthesis
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Cholestanes / chemistry
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Cholestanes / pharmacology*
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Cyclooxygenase 2 / genetics
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Cyclooxygenase 2 / metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Ear Diseases / drug therapy*
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Ear Diseases / metabolism
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Edema / drug therapy*
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Edema / metabolism
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Inflammation / drug therapy*
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Inflammation / metabolism
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Interleukin-6 / genetics
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Interleukin-6 / metabolism
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Macrophages / drug effects
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Macrophages / metabolism
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Male
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Mice
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Molecular Structure
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Oximes / chemical synthesis
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Oximes / chemistry
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Oximes / pharmacology*
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Structure-Activity Relationship
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Cholestanes
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Interleukin-6
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Oximes
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Tumor Necrosis Factor-alpha
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Cyclooxygenase 2