密流烷素（miliusanes）是一类抗癌活性的前导分子，属于从密花属植物中分离得到的交联萜类（meroterpenoids）化合物，具有18个碳的骨架。本研究对华密木（Miliusa sinensis）进行了植物化学研究，以发现具有多样结构特征的新密流烷素，以更好地理解它们的结构活性关系。结果从该植物的枝叶中分离和鉴定出20个化合物，包括两个亚类（sub-classes）的密流烷素中的12个新成员（7-14 和 17-20）。通过光谱分析和电子圆二色性（electronic circular dichroism）确定了这些化合物的结构，包括绝对构型。通过密流醇 (1) 的单晶X射线衍射分析，首次确认了密流烷素结构的绝对立体化学（absolute stereochemistry）。生物活性评估显示，部分密流烷素具有较强的抑制人类癌细胞系生长的活性，其IC50值范围为0.52到23.5 μM。虽然化合物11的结构中包含一个非共轭的1,4-二酮系统，但在胃癌细胞中表现出比已知的密流醇（1）更强的细胞毒活性，为密流烷素添加了一个新的结构活性特征。初步的作用机制研究表明，密流烷素可能是一类双重细胞迁移抑制剂和细胞衰老诱导剂。版权所有 © 2023 Elsevier Inc. 保留所有权利。

Miliusanes are a class of anticancer lead molecules belonging to meroterpenoids with an 18-carbon skeleton isolated from Miliusa plants. A phytochemical study of the plant M. sinensis was carried out to discover new miliusanes with diverse structural features in order to better understand their structure-activity relationship. As a result, 20 compounds including 12 new ones (7-14 and 17-20) belonging to two sub-classes of miliusanes were isolated and identified from the twigs and leaves of this plant. Their structures, including absolute configurations, were determined by spectroscopic analyses and electronic circular dichroism. The absolute stereochemistry of miliusane structures has also been confirmed for the first time through the single crystal X-ray diffraction analysis of miliusol (1). Bioactivity evaluation showed that some of the miliusane isolates potently inhibit cell growth of several human derived cancer cell lines with IC50 values ranging from 0.52 to 23.5 μM. Compound 11 demonstrated more potent cytotoxic activity than the known miliusol (1) in stomach cancer cells though its structure contains an unconjugated 1, 4-diketone system, which added a new structure-activity feature to miliusanes. The preliminary mechanism of action studies revealed that they could be a class of dual cell migration inhibitor and senescence inducer.Copyright © 2023 Elsevier Inc. All rights reserved.