Natural products dispirocochlearoids A-C, which are meroterpenoids derived from 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 ) exhibiting strong inhibitory activity against IL-1β expression in lipopolysaccharide-stimulated bone marrow-derived macrophage cells (IC = 2.8 μM).
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Synthesis and Biological Activity of Tetracyclic Dispiro Core Derivatives of Natural Products Dispirocochlearoids A-C.
Org Lett
November 2024
Shandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery, Yantai, Shandong 264117, China.
Natural products dispirocochlearoids A-C, which are meroterpenoids derived from 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 ) exhibiting strong inhibitory activity against IL-1β expression in lipopolysaccharide-stimulated bone marrow-derived macrophage cells (IC = 2.
View Article and Find Full Text PDFMetabolites as Probes to Identify a COX-2 Active Site and as in Vitro and in Vivo Anti-Inflammatory Agents.
Org Lett
April 2020
School of Pharmaceutical Sciences, School of Medicine, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen 518060, P. R. China.
(±)-Dispirocochlearoids A-C (-), meroterpenoids with a 6/6/5/6/6/6 ring system, were isolated from . - are selective COX-2 inhibitors with an IC value of (-)- at 386 nM. Site-directed mutagenesis identified His351 as a COX-2 active site.
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