School of Traditional Chinese Materia Medica, Key Laboratory of Computational Chemistry-Based Natural Antitumor Drug Research & Development, Liaoning Province, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
Chinese People's Liberation Army 210 Hospital, Dalian 116021, People's Republic of China.
Bioorg Chem. 2019 Mar;84:309-318. doi: 10.1016/j.bioorg.2018.11.049. Epub 2018 Nov 28.
Seven new tirucallane-type triterpenoids (1-7), kumuquassin A-G, along with 20 known analogues (8-27) were isolated from the stems of Picrasma quassioides. The structures and the absolute configurations of new compounds were elucidated by spectroscopic data, electronic circular dichroism (ECD) spectroscopic analyses and quantum ECD calculations. Notably, kumuquassin A (1) contains a rare Δ double bond, kumuquassin B (2) is the first example of tirucallane triterpenoid possessing a 5/3 biheterocyclic ring system at the side chain. All the compounds were screened for the cytotoxicity against two human hepatoma cell lines, HepG2 and Hep3B, and several compounds exhibited promising activity. The most potential compound 3 was selected for cell cycle analysis, which showed that 3 could cause an accumulation of HepG2 cells at subG1 peak. Annexin V-FITC/PI staining further confirmed that compound 3 caused death of hepatoma cells through apoptosis induction.
从苦槛蓝的茎中分离得到了 7 种新的雷公烷型三萜（1-7），包括苦槛蓝 A-G，以及 20 种已知的类似物（8-27）。通过光谱数据、电子圆二色性（ECD）光谱分析和量子 ECD 计算阐明了新化合物的结构和绝对构型。值得注意的是，苦槛蓝 A（1）含有罕见的Δ双键，苦槛蓝 B（2）是第一个具有侧链 5/3 双杂环系统的雷公烷型三萜。所有化合物均进行了对两种人肝癌细胞系 HepG2 和 Hep3B 的细胞毒性筛选，其中一些化合物表现出有希望的活性。选择最有潜力的化合物 3 进行细胞周期分析，结果表明 3 可使 HepG2 细胞在 subG1 峰处积累。Annexin V-FITC/PI 染色进一步证实，化合物 3 通过诱导细胞凋亡导致肝癌细胞死亡。
