Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan Flustra foliacea,Journal of Natural Products

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Bromotryptamine and Imidazole Alkaloids with Anti-inflammatory Activity from the Bryozoan Flustra foliacea
Journal of Natural Products ( IF 3.3 ) Pub Date : 2020-10-05 , DOI: 10.1021/acs.jnatprod.0c00126
Xiaxia Di ₁ , Shuqi Wang ₂ , Jon T Oskarsson ₃ , Caroline Rouger ₄ , Deniz Tasdemir _{4,

5} , Ingibjorg Hardardottir _{3,

6} , Jona Freysdottir _{3,

6} , Xiao Wang ₇ , Tadeusz F Molinski ₈ , Sesselja Omarsdottir ₁

Affiliation

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.

中文翻译：

来自苔藓虫的具有抗炎活性的溴色胺和咪唑生物碱

对冰岛采集的海洋苔藓虫Flustra foliacea进行的化学研究分离出 13 种新的溴色胺生物碱，氟曲胺 Q–W ( 1 – 7 ) 和氟曲胺醇 C–H ( 8 – 13 )，以及两种新的咪唑生物碱，氟曲咪唑 A 和 B ( 14和15 )，以及 12 种先前描述的化合物 ( 16 – 27 )。它们的结构是通过使用 1D 和 2D NMR 以及 HRESIMS 进行详细的光谱分析来确定的。使用密度泛函理论计算¹³ C 和¹ H NMR 化学位移来验证结构2 。除了化学衍生化之外，还根据耦合常数分析、NOESY、[α] _D和 ECD 光谱数据阐明了新化合物的相对和绝对构型。使用树突状细胞模型测试这些化合物的体外抗炎活性。八种化合物（ 1 , 3 , 5 , 13 , 16 , 18 , 26和27 ）减少树突状细胞促炎细胞因子 IL-12p40 的分泌，两种化合物（ 4和14 ）增加抗炎细胞因子的分泌。 IL-10。 Deformylflustrabromine B ( 27 ) 显示出最有效的抗炎作用 (IC ₅₀ 2.9 μM)。这些结果表明，来自冰岛的F. foliacea表达了广泛的溴化生物碱，其中许多生物碱在结构上没有先例。代谢物27具有强大的体外抗炎活性，值得进一步研究其作为炎症相关疾病先导药物的潜力。

更新日期：2020-10-26

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