TY - JOUR
T1 - Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan Flustra foliacea
AU - Harðardóttir, Ingibjörg
AU - Di, Xiaxia
AU - Wang, Shuqi
AU - Óskarsson, Jón Þórir
AU - Rouger, Caroline
AU - Tasdemir, Deniz
AU - Freysdóttir, Jóna
AU - Wang, Xiao
AU - Molinski, Tadeusz F.
AU - Ómarsdóttir, Sesselja Sigurborg
N1 - Funding Information: Financial support was received from the University of Iceland Research Fund (Doctoral Grant) and AVS R&D Fund of The Ministry of Fisheries and Agriculture in Iceland. The authors would like to thank Dr. H. T. Rapp at the University of Bergen for the identification of animal material. Publisher Copyright: ©
PY - 2020/10/23
Y1 - 2020/10/23
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85094221987&partnerID=8YFLogxK
U2 - 10.1021/acs.jnatprod.0c00126
DO - 10.1021/acs.jnatprod.0c00126
M3 - Article
C2 - 33016699
SN - 0163-3864
VL - 83
SP - 2854
EP - 2866
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 10
ER -