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

• Published in: Journal of Natural Products
• Main Authors: Di, Xiaxia, Wang, Shuqi, Oskarsson, Jon T, Rouger, Caroline, Tasdemir, Deniz, Hardardottir, Ingibjorg, Freysdottir, Jona, Wang, Xiao, Molinski, Tadeusz F, Omarsdottir, Sesselja
• Other Authors: 1Faculty of Pharmaceutical Sciences, University of Iceland, IS-107 Reykjavik, Iceland. 2Faculty of Pharmaceutical Science, Shandong University, 250012 Jinan, China. 3Department of Immunology, Landspitali-The National University Hospital of Iceland, IS-101 Reykjavik, Iceland. 4GEOMAR Centre for Marine Biotechnology (GEOMAR-Biotech), Marine Natural Products Chemistry Research Unit, GEOMAR Helmholtz Centre for Ocean Research Kiel, 24106 Kiel, Germany. 5Faculty of Mathematics and Natural Sciences, Kiel University, 24118 Kiel, Germany. 6Faculty of Medicine, Biomedical Center, University of Iceland, IS-101 Reykjavik, Iceland. 7Analytical Research & Development, Merck & Co. Inc, Rahway, New Jersey 07065, United States. 8Department of Chemistry and Biochemistry and Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, 9500 Gilman Drive, La Jolla, California 92093, United States.
• Format: Article in Journal/Newspaper
• Language: English
• Published: American Society of Pharmacognosy 2021
• Subjects: Bromotryptamine; Alkalóíðar; Alkaloids; Aquatic Organisms; Iceland
• Online Access: http://hdl.handle.net/2336/621620; https://doi.org/10.1021/acs.jnatprod.0c00126

To access publisher's full text version of this article click on the hyperlink below Chemical investigation of the marine bryozoan Flustra foliacea collected in Iceland resulted in isolation of 13 new bromotryptamine alkaloids, flustramines Q-W (1-7) and flustraminols C-H (8-13), and two new imidazole alkaloids, flustrimidazoles A and B (14 and 15), together with 12 previously described compounds (16-27). Their structures were established by detailed spectroscopic analysis using 1D and 2D NMR and HRESIMS. Structure 2 was verified by calculations of the 13C and 1H 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]D, and ECD spectroscopic data, in addition to chemical derivatization. The compounds were tested for in vitro anti-inflammatory activity using a dendritic cell model. Eight compounds (1, 3, 5, 13, 16, 18, 26, and 27) decreased dendritic cell secretion of the pro-inflammatory cytokine IL-12p40, and two compounds (4 and 14) increased secretion of the anti-inflammatory cytokine IL-10. Deformylflustrabromine B (27) showed the most potent anti-inflammatory effect (IC50 2.9 μM). These results demonstrate that F. foliacea from Iceland expresses a broad range of brominated alkaloids, many without structural precedents. The potent anti-inflammatory activity in vitro of metabolite 27 warrants further investigations into its potential as a lead for inflammation-related diseases. University of Iceland AVS R&D Fund of The Ministry of Fisheries and Agriculture in Iceland