Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan .

Chemical investigation of the marine bryozoan collected in Iceland resulted in isolation of 13 new bromotryptamine alkaloids, flustramines Q-W (-) and flustraminols C-H (-), and two new imidazole alkaloids, flustrimidazoles A and B ( and ), together with 12 previously described compounds (-). Their structures were established by detailed spectroscopic analysis using 1D and 2D NMR and HRESIMS. Structure was verified by calculations of the C and H NMR chemical shifts using density functional theory. The relative and absolute configurations of the new compounds were elucidated on the basis of coupling constant analysis, NOESY, [α], and ECD spectroscopic data, in addition to chemical derivatization. The compounds were tested for anti-inflammatory activity using a dendritic cell model. Eight compounds (, , , , , , , and ) decreased dendritic cell secretion of the pro-inflammatory cytokine IL-12p40, and two compounds ( and ) increased secretion of the anti-inflammatory cytokine IL-10. Deformylflustrabromine B () showed the most potent anti-inflammatory effect (IC 2.9 μM). These results demonstrate that from Iceland expresses a broad range of brominated alkaloids, many without structural precedents. The potent anti-inflammatory activity of metabolite warrants further investigations into its potential as a lead for inflammation-related diseases.