Faculty of Pharmaceutical Sciences, University of Iceland, IS-107 Reykjavik, Iceland.
Faculty of Pharmaceutical Science, Shandong University, 250012 Jinan, China.
J Nat Prod. 2020 Oct 23;83(10):2854-2866. doi: 10.1021/acs.jnatprod.0c00126. Epub 2020 Oct 5.
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.
从冰岛采集的海鞘中进行的化学研究导致分离出 13 种新的溴色胺生物碱，包括 flustramines Q-W (-) 和 flustraminols C-H (-)，以及两种新的咪唑生物碱，flustrimidazoles A 和 B ( 和 )，以及 12 种先前描述的化合物 (-)。通过使用 1D 和 2D NMR 和 HRESIMS 的详细光谱分析确定了它们的结构。通过使用密度泛函理论计算 C 和 H NMR 化学位移，验证了结构 。根据偶合常数分析、NOESY、[α] 和 ECD 光谱数据以及化学衍生化，确定了新化合物的相对和绝对构型。测试了这些化合物在树突状细胞模型中的抗炎活性。八种化合物（，，，，，，，和）降低了树突状细胞分泌促炎细胞因子 IL-12p40 的水平，两种化合物（和）增加了抗炎细胞因子 IL-10 的分泌。去甲氟斯他溴素 B () 表现出最强的抗炎作用（IC 2.9 μM）。这些结果表明，来自冰岛的海鞘表达了广泛的溴化生物碱，其中许多没有结构先例。代谢物 的强抗炎活性表明其作为炎症相关疾病的潜在先导化合物值得进一步研究。
