Dysivillosins A-D, Unusual Anti-allergic Meroterpenoids from the Marine Sponge Dysidea villosa.

ABSTRACT: Four unusual meroterpenoids, dysivillosins A-D (1-4), were isolated from an organic extract of the marine sponge Dysidea villosa collected from the South China Sea. Their planar structures were determined by 1D and 2D NMR and HRESIMS techniques, while the relative and absolute configurations were elucidated by NOESY experiments and comparison between the calculated and experimental ECD spectra. To the best of our knowledge, dysivillosins A-D are the first examples of terpene-polyketide-pyridine hybrid metabolites from the nature. Anti-allergic activity evaluation showed that compounds 1-4 potently inhibited the release of ?-hexosaminidase, a marker of degranulation, in a dose-dependent manner with IC₅₀ values of 8.2-19.9??M. Additionally, the four meroterpenoids could downregulate the production of lipid mediator leukotrienes B₄ (LTB₄) and pro-inflammatory cytokine interleukin-4 (IL-4) in the antigen-stimulated RBL-2H3 mast cells. Further biological investigations revealed that dysivillosin A (1) could suppress the phosphorylation of Syk and PLC?1 in IgE/Fc?RI/Syk signaling pathway, which resulted in the inhibition of degranulation and the downregulation of LTB₄ and IL-4 production in mast cells.

SUBMITTER: Jiao WH 

PROVIDER: S-EPMC5567184 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature