State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
State Key Laboratory of Digestive Health, Institute of Materia Medica, Chinses Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Bioorg Chem. 2024 Oct;151:107691. doi: 10.1016/j.bioorg.2024.107691. Epub 2024 Aug 3.
Ten new B-ring aromatized 6/6/6-tricyclic dearomatized benzocogeijerene-based meroterpenoids with unusual methyl 1,2-shift or demethylation (2-9b), and two new geranylquinol derivatives (1 and 10), together with two known compounds (11 and 12), were isolated from the roots of Arnebia euchroma. Their structures were elucidated by extensive spectroscopic methods, X-ray diffraction crystallography, and ECD calculations. The plausible biosynthetic pathways including the unusual methyl 1,2-shfit and demethylation for B-ring aromatized 6/6/6-tricyclic meroterpenoids were discussed. Compounds 1, 2, 5, 6, 11, and 12 showed significant cardioprotective activities comparable to diltiazem against isoprenaline (ISO)-induced H9C2 cell damage in vitro. Compound 11 probably exerted heart-protective effect on ISO-induced H9C2 cells by modulating the PI3K-AKT-mTOR pathway, reducing excessive autophagy, and decreasing myocardial apoptosis.
从秀丽马先蒿（Arnebia euchroma）的根部分离得到了 10 个新的 B 环芳构化 6/6/6-三环去芳构化苯并[c]庚二烯基倍半萜类化合物，具有不寻常的甲基 1,2-迁移或去甲基化（2-9b），以及两个新的香叶基喹啉衍生物（1 和 10），以及两个已知化合物（11 和 12）。通过广泛的光谱方法、X 射线衍射晶体学和 ECD 计算确定了它们的结构。讨论了包括 B 环芳构化 6/6/6-三环倍半萜类化合物不寻常的甲基 1,2-迁移和去甲基化的可能生物合成途径。化合物 1、2、5、6、11 和 12 对异丙肾上腺素（ISO）诱导的 H9C2 细胞损伤显示出与地尔硫卓相当的显著的心脏保护活性。化合物 11 可能通过调节 PI3K-AKT-mTOR 通路、减少过度自噬和减少心肌细胞凋亡，对 ISO 诱导的 H9C2 细胞发挥心脏保护作用。
