青蒿（Artemisia annua L.）是一种著名的中药材，用于治疗疟疾和多种肿瘤。我们的初步筛选表明，青蒿的 EtOAc 提取物对 HepG2、Huh7 和 SK-Hep-1 细胞系具有活性，在 200 μg/mL 浓度下，抑制率分别为 53.2%、52.1% 和 59.6%。通过生物测定引导分离青蒿，得到了 14 种不寻常的涉及杜松烷的倍半萜二聚体，即青蒿素 A-N (1-14)，其结构通过广泛的光谱分析、ECD 计算和单晶 X 射线衍射得以阐明。在结构上，根据两种单体倍半萜类化合物的偶联模式，这些化合物被分为五种不同的类型。其中，化合物1-9代表了通过两个5(4→3)-abeo-cadinane倍半萜单体的C-3-C-3'单键形成的倍半萜二聚体的第一个例子，而化合物13和14是融合的二聚体由杜松烷和葎草烷倍半萜类化合物通过酯键形成。 1、4、6 和 8 的甲基化衍生物对 HepG2、Huh7 和 SK-Hep-1 细胞系表现出抗肝癌活性，IC50 值范围为 30.5 至 57.2 μM。版权所有 © 2024。由 Elsevier Ltd 出版。

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 IC50 values ranging from 30.5 to 57.2 μM.Copyright © 2024. Published by Elsevier Ltd.