State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, PR China.
Phytochemistry. 2024 Jun;222:114100. doi: 10.1016/j.phytochem.2024.114100. Epub 2024 Apr 16.
Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC values ranging from 7.9 to 67.1 μM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 μM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide K value of 43.7 μM by Surface Plasmon Resonance assay.
从 Artemisia myriantha var. pleiocephala（菊科）中分离得到 Artemyriantholides A-K（1-11）以及 14 种已知化合物（12-25）。通过单晶 X 射线衍射分析确定了化合物 2 和 8-9 的结构和绝对构型，通过 MS、NMR 光谱数据和电子圆二色谱计算确定了其他化合物的结构。所有化合物均被化学表征为愈创木烷型倍半萜二聚体（GSD）。化合物 1 是通过 C-3/C-11'和 C-5/C-13'键连接的 GSD 的首例，化合物 2 和 5 是含有氯原子的罕见 GSD。通过抗肝癌测定，11 种化合物在 HepG2、Huh7 和 SK-Hep-1 细胞系中表现出明显的抑制活性，提供的 IC 值范围为 7.9 至 67.1μM。重要的是，化合物 5 和 8 表现出最好的抑制活性，IC 值分别为 14.2 和 18.8（HepG2）、9.0 和 11.5（Huh7）以及 8.8 和 11.3μM（SK-Hep-1）。通过计算预测模型，预测化合物 5 的靶标为 MAP2K2。进行了化合物 5 与 MAP2K2 的相互作用实验，通过分子对接得到-9.0kcal/mol 的对接评分，并通过表面等离子体共振分析得到 43.7μM 的 K 值。
