6-Bromoindole Derivatives from the Icelandic Marine Sponge : Isolation and Anti-Inflammatory Activity.

An UPLC-qTOF-MS-based dereplication study led to the targeted isolation of seven bromoindole alkaloids from the sub-Arctic sponge . This includes three new metabolites, namely geobarrettin A⁻C (⁻) and four known compounds, barettin (), 8,9-dihydrobarettin (), 6-bromoconicamin (), and l-6-bromohypaphorine () The chemical structures of compounds ⁻ were elucidated by extensive analysis of the NMR and HRESIMS data. The absolute stereochemistry of geobarrettin A () was assigned by ECD analysis and Marfey's method employing the new reagent l--(1-fluoro-2,4-dinitrophenyl)tryptophanamide (l-FDTA). The isolated compounds were screened for anti-inflammatory activity using human dendritic cells (DCs). Both and reduced DC secretion of IL-12p40, but concomitantly increased IL-10 production. Maturing DCs treated with or before co-culturing with allogeneic CD4⁺ T cells decreased T cell secretion of IFN-γ, indicating a reduction in Th1 differentiation. Although barettin () reduced DC secretion of IL-12p40 and IL-10 (IC values 11.8 and 21.0 μM for IL-10 and IL-12p40, respectively), maturing DCs in the presence of did not affect the ability of T cells to secrete IFN-γ or IL-17, but reduced their secretion of IL-10. These results indicate that and may be useful for the treatment of inflammation, mainly of the Th1 type.