Abstract
Natural products dispirocochlearoids A-C, which are meroterpenoids derived from Ganoderma fungi, feature a 6/6/5/6/6/6 ring system and exhibit selective COX-2 inhibitory activity. Herein, the concise total synthesis of the tetracyclic core structure of dispirocochlearoids A-C was achieved through an aldol reaction/cyclization/deprotection/cyclization cascade sequence. A series of simplified tetracyclic analogues was successfully constructed and their anti-inflammatory activity was further explored, with several tetracyclic analogues (such as compound 8ab) exhibiting strong inhibitory activity against IL-1β expression in lipopolysaccharide-stimulated bone marrow-derived macrophage cells (IC50 = 2.8 μM).
MeSH terms
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Animals
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Anti-Inflammatory Agents / chemical synthesis
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Anti-Inflammatory Agents / chemistry
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Anti-Inflammatory Agents / pharmacology
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Biological Products* / chemical synthesis
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Biological Products* / chemistry
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Biological Products* / pharmacology
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Cyclization
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Cyclooxygenase 2 Inhibitors / chemical synthesis
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Cyclooxygenase 2 Inhibitors / chemistry
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Cyclooxygenase 2 Inhibitors / pharmacology
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Ganoderma / chemistry
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Interleukin-1beta / antagonists & inhibitors
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Interleukin-1beta / metabolism
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Lipopolysaccharides* / antagonists & inhibitors
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Lipopolysaccharides* / pharmacology
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Macrophages* / drug effects
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Mice
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Molecular Structure
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Structure-Activity Relationship
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Terpenes / chemical synthesis
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Terpenes / chemistry
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Terpenes / pharmacology
Substances
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Biological Products
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Lipopolysaccharides
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Interleukin-1beta
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Anti-Inflammatory Agents
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Terpenes
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Cyclooxygenase 2 Inhibitors