He Xiao-Feng, Li Tian-Ze, Ma Yun-Bao, Wang Meng-Fei, Chen Ji-Jun
State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, 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; University of Chinese Academy of Sciences, Beijing, 100049, PR China.
Phytochemistry. 2024 Oct;226:114216. doi: 10.1016/j.phytochem.2024.114216. Epub 2024 Jul 6.
Artemisia annua L. ("Qinghao" in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 μg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1-14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1-9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3' single bond of two 5(4 → 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC values ranging from 30.5 to 57.2 μM.
青蒿（中国名为“青蒿”）是一种著名的传统中草药，一直用于治疗疟疾和各种肿瘤。我们的初步筛选表明，青蒿的乙酸乙酯提取物对HepG2、Huh7和SK-Hep-1细胞系具有活性，在200μg/mL时的抑制率分别为53.2%、52.1%和59.6%。通过生物活性导向的分离方法从青蒿中得到了14个结构独特的含杜松烷倍半萜二聚体，即青蒿素A‒N（1-14），其结构通过广泛的光谱分析、电子圆二色光谱计算和单晶X射线衍射得以阐明。从结构上看，这些化合物根据两个单体倍半萜的偶联方式分为五种不同类型。其中，化合物1-9是通过两个5(4→3)-去甲杜松烷倍半萜单体的C-3‒C-3'单键形成的倍半萜二聚体的首例，而化合物13和14是杜松烷和葎草烷倍半萜通过酯键稠合而成的二聚体。化合物1、4、6和8的甲基化衍生物对HepG2、Huh7和SK-Hep-1细胞系显示出抗肝癌活性，IC值范围为30.5至57.2μM。
