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新疆阿魏中的倍半萜香豆素及其细胞毒活性。

Sesquiterpene coumarins from Ferula sinkiangensis K.M.Shen and their cytotoxic activities.

机构信息

The Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.

Xinjian Institute of Chinese Materia Medica and Ethical Materia Medica, Urumqi, 830002, China.

出版信息

Phytochemistry. 2020 Dec;180:112531. doi: 10.1016/j.phytochem.2020.112531. Epub 2020 Sep 30.

Abstract

Five undescribed sesquiterpene coumarins, one undescribed coumarin derivative, and twenty-five known analogues, were isolated from the resin of Ferula sinkiangensis K.M.Shen. The planar structures and relative configurations of the undescribed compounds were determined by NMR experiment and HRESIMS data. The absolute configurations were established by Electrostatic Circular Dichroism method. Among these analogues, Sinkiangenol E showed the best cytotoxic activity against HeLa cervical cancer cells. Annexin V-FITC/PI staining indicated that Sinkiangenol E induced apoptosis in HeLa cells. Cell cycle analysis showed Sinkiangenol E arrested cell cycle at G0/G1 phase. Western blot results proved that Sinkiangenol E affected apoptosis-related and cell cycle regulation-related protein expression by activating the MAPK pathway.

摘要

从新疆阿魏树脂中分离得到了 5 个未被描述的倍半萜香豆素、1 个未被描述的香豆素衍生物和 25 个已知类似物。通过 NMR 实验和 HRESIMS 数据确定了未知化合物的平面结构和相对构型。通过电动力学圆二色法确定了绝对构型。在这些类似物中,Sinkiangenol E 对宫颈癌 HeLa 细胞表现出最好的细胞毒性活性。Annexin V-FITC/PI 染色表明 Sinkiangenol E 诱导 HeLa 细胞凋亡。细胞周期分析表明 Sinkiangenol E 通过激活 MAPK 通路将细胞周期阻滞在 G0/G1 期。Western blot 结果证明,Sinkiangenol E 通过激活 MAPK 通路影响与细胞凋亡和细胞周期调控相关的蛋白表达。

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