Key Laboratory of Computational Chemistry Based Natural Antitumor Drug Research & Development, Liaoning Province, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang, 110016, People's Republic of China.
Eur J Med Chem. 2020 Jul 15;198:112362. doi: 10.1016/j.ejmech.2020.112362. Epub 2020 Apr 25.
Chromatographic purification of Elephantopus scaber led to 16 new germacrane-type sesquiterpene lactones (1-16), named elephantopinolide A-P, along with a known analogue (17). Their structures were confirmed by comprehensive spectroscopic analyses, single-crystal X-ray diffraction, and comparison between the experimental and calculated ECD spectra. Their hepatocellular inhibition activities against Hep3B and HepG2 cells were screened by MTT assay, and the structure-activity relationships were examined. The results revealed that 10 (IC value of 2.83 μM and 1.98 μM) is more potent than sorafenib. The underlying mechanism study demonstrated that 10 could markedly induce apoptosis accompanied by increased ROS production and decreased mitochondrial membrane potential, resulting in the autophagy and G2/M phase cell arrest in Hep3B and HepG2 cells. Furthermore, signal pathways including MAPKs and AKT may play important roles in 10-induced hepatocellular carcinoma cells death.
色谱纯化鬼针草得到 16 个新的大根香叶型倍半萜内酯（1-16），命名为 elephantopinolide A-P，以及一个已知的类似物（17）。它们的结构通过综合光谱分析、单晶 X 射线衍射和实验与计算 ECD 光谱的比较来确定。通过 MTT 测定法筛选了它们对 Hep3B 和 HepG2 细胞的肝细胞抑制活性，并研究了结构-活性关系。结果表明，10（IC 值为 2.83 μM 和 1.98 μM）比索拉非尼更有效。基础机制研究表明，10 能显著诱导细胞凋亡，同时增加 ROS 产生和降低线粒体膜电位，导致 Hep3B 和 HepG2 细胞自噬和 G2/M 期细胞停滞。此外，MAPKs 和 AKT 等信号通路可能在 10 诱导的肝癌细胞死亡中发挥重要作用。
