Tuberatolides, Potent FXR Antagonists from the Korean Marine Tunicate Botryllus tuberatus
Tuberatolides, Potent FXR Antagonists from the Korean Marine Tunicate Botryllus tuberatus
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DOI：
10.1021/np100489u
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发表时间：
2011-01-01
影响因子：
5.1
通讯作者：
Kang, Heonjoong
中科院分区：
文献类型：
--
作者：
Choi, Hyukjae;Hwang, Hoosang;Kang, Heonjoong
从朝鲜海洋被囊动物Botryllus tuberatus中分离得到1个类异戊二烯化合物tuberatrium A（1）、2 '-epi-tuberatrium B（2）和2'-epi-tuberatrium B（3）以及已知的3个类萜化合物yezoquinolide（4）、（R）-sargachromenol（5）和（S）-sargachromenol（6）。化合物的结构经核磁共振、质谱和圆二色谱确证。这些萜类化合物拮抗鹅去氧胆酸（CDCA）激活的人法尼醇X受体（hFXR）在基于细胞的共转染试验与IC 50值低至1.5 μ M，对类固醇受体没有显着的影响。此外，他们在无细胞表面等离子体共振实验中从CDCA结合的hFXR配体结合结构域释放共激活肽。
One isoprenoid, tuberatolide A (1), meroterpenoids tuberatolide B (2) and 2'-epi-tuberatolide B (3), and the known meroterpenoids yezoquinolide (4), (R)-sargachromenol (5), and (S)-sargachromenol (6) were isolated from the Korean marine tunicate Botryllus tuberatus. The structures of these compounds were elucidated by NMR, MS, and CD spectroscopic analyses. These terpenoids antagonized the chenodeoxycholic acid (CDCA)-activated human farnesoid X receptor (hFXR) in a cell-based co-transfection assay with IC50 values as low as 1.5 mu M without significant effect on steroid receptors. Furthermore, they released the co-activator peptide from the CDCA-bound hFXR ligand binding domain in cell-free surface plasmon resonance experiments.