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Studies On The Anti-Inflammatory Constituents Of Marine Natural Products

Posted on:2015-10-08Degree:MasterType:Thesis
Country:ChinaCandidate:X CuiFull Text:PDF
GTID:2284330431979943Subject:Medicinal chemistry
Abstract/Summary:PDF Full Text Request
In this study, we isolated a new sulfonic acid derivative,(Z)-4-methylundeca-1,9-diene-6-sulfonic acid (1), from the sea urchin collected from the Sea of Okhotsk. We established the structure of this new compound by analysis of NMR and HRMS data, along with comparison of the data with those of the related compounds reported in the literature. In addition, we investigated its anti-inflammatory effects in LPS-stimulated RAW264.7macrophages. Compound1inhibited the production of NO, iNOS, PGE2, and COX-2, and it also suppressed the production of pro-inflammatory cytokines, such as TNF-a and IL-1β.It inhibited the translocation of the NF-κB subunit p65into the nucleus by interrupting the phosphorylation and degradation of IκB-α In addition, compound1significantly decreased the phosphorylation of JNK and p38in LPS-stimulated RAW264.7macrophages, suggesting that suppression of the inflammation process by compound1was mediated through the MAPK pathway. Taken together, this study showed that the anti-inflammatory effects of a new sulfonic acid derivative,(Z)-4-methylundeca-1,9-diene-6-sulfonic acid were mediated through the inhibition of NF-κB and JNK/p38MAPK signaling pathways.In the course of a bioassay-guided study of metabolites from the marine fungus Eurotium sp. SF-5989, two diketopiperazine type indole alkaloids, neoechinulins A and B, were isolated. In this study, we investigated the anti-inflammatory effects of neoechinulins A (2) and B (3) on lipopolysaccharide (LPS)-stimulated RAW264.7macrophages. The anti-inflammatory effect of neoechinulin A (2) in LPS-stimulated RAW264.7macrophages were due to the inhibition of the NF-κB and p38MAPK pathways. On the other hand, neoechinulin B (3) affected the cell viability at25μM although the compound displayed similar inhibitory effect of NO production to neoechinulin A (2) at lower doses.
Keywords/Search Tags:(Z)-4-methylundeca-1,9-diene-6-sulfonic acid, neoechinulin A, RAW264.7macrophages, inflammation, NF-κB
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