Su Lihua, Zhang Xintian, Ma Yunbao, Geng Changan, Huang Xiaoyan, Hu Jing, Li Tianze, Tang Shuang, Shen Cheng, Gao Zhen, Zhang Xuemei, Chen Ji-Jun
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming 650201, China.
University of Chinese Academy of Sciences, Beijing 100049, China.
Acta Pharm Sin B. 2021 Jun;11(6):1648-1666. doi: 10.1016/j.apsb.2020.12.006. Epub 2020 Dec 15.
Leading by cytotoxicity against HepG2 cells, bioactivity-guided fractionation of the EtOAc fraction from led to the isolation of 18 new guaianolide dimers, artematrolides A-R and lavandiolides A, B, C, H, and J. Eight compounds (, , , , , and -) were unambiguously confirmed by the single-crystal X-ray diffraction analyses, and the others were elucidated based on IR, UV, HRESIMS, 1D and 2D NMR experiments, and comparison of the experimental and calculated ECD data. Structurally, all of them were [4 + 2] Diels-Alder adducts of two monomeric guaianolides. The isolates were evaluated for their cytotoxicity against three human hepatoma cell lines, and 19 compounds demonstrated cytotoxicity against HepG2, SMMC-7721, and Huh7 cell lines. Especially, compounds , , , and exhibited cytotoxicity with IC values of 4.4, 3.8, 7.6, and 6.7 μmol/L (HepG2), 9.6, 4.6, 6.6, and 6.0 μmol/L (SMMC-7721), and 7.6, 4.5, 6.9, and 5.6 μmol/L (Huh7), respectively. Notably, compound showed the most promising activity against three human hepatoma cell lines and dose-dependently inhibited cell migration and invasion, induced G2/M cell cycle arrest and cell apoptosis in HepG2 cells, down-regulated the expression of BCL-2 and PARP-1, and activated PARP-1 to up-regulate the expression of cleaved-PARP-1.
以对HepG2细胞的细胞毒性为导向，对[来源]的乙酸乙酯馏分进行生物活性导向的分离，得到了18个新的愈创木烷型二萜二聚体，即青蒿三醇A - R以及薰衣草二醇A、B、C、H和J。8个化合物（[具体化合物]）通过单晶X射线衍射分析得到明确确认，其他化合物则通过红外光谱（IR）、紫外光谱（UV）、高分辨电喷雾电离质谱（HRESIMS）、一维和二维核磁共振实验以及实验和计算的电子圆二色光谱（ECD）数据比较进行鉴定。从结构上看，它们均为两个单体愈创木烷型二萜的[4 + 2]狄尔斯 - 阿尔德加成物。对分离得到的化合物进行了针对三种人肝癌细胞系的细胞毒性评估，19个化合物对HepG2、SMMC - 7721和Huh7细胞系表现出细胞毒性。特别是，化合物[具体化合物]表现出细胞毒性，其对HepG2、SMMC - 7721和Huh7细胞系的半数抑制浓度（IC）值分别为4.4、3.8、7.6和6.7 μmol/L（HepG2），9.6、4.6、6.6和6.0 μmol/L（SMMC - 7721），以及7.6、4.5、6.9和5.6 μmol/L（Huh7）。值得注意的是，化合物[具体化合物]对三种人肝癌细胞系表现出最有前景的活性，并剂量依赖性地抑制细胞迁移和侵袭，诱导HepG2细胞的G2/M期细胞周期阻滞和细胞凋亡，下调BCL - 2和PARP - 1的表达，并激活PARP - 1以上调裂解型PARP - 1的表达。
Zotero 插件
