Artemisianins A-D (1-4), four stereoisomers of sesquiterpenoid dimers, forming via [4+2] cycloaddition from a 1, 10-seco-guaianolide dienophile and a guaianolide diene, along with two biosynthetically related precurors 5 and 6, were isolated from the famous traditional Chinese medicine Artemisia argyi. The structures of 1-4, including their absolute configurations, were elucidated by extensive spectroscopic data and ECD/TDDFT calculation analysis. Compounds 1-4 exhibited cytotoxicity with IC50 values ranging from 7.2 to 23.3 μM. The accumulation of Ca2+ in cytoplasm and enlarged endoplasmic reticulum (ER) indicated that 1 mediated HT-29 cancer cell apoptosis through improvement of ER-stress, which was further proved by unfolded protein response (UPR) pathway on basis of the upregulation of IRE1α, p-PERK, ATF6, and CHOP.

中文翻译：

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青蒿素的新立体异构体青蒿素AD，涉及来自艾蒿的异二聚体[4 + 2]加合物，通过增强内质网应激诱导凋亡。

从1，10-癸二酸-愈创木酚内酯二烯亲和体和愈创木酚内酯二烯经[4 + 2]环加成反应形成的四倍体萜类化合物二元立体异构体青蒿素AD（1-4），从两个生物合成相关的前体5和6中分离出来。著名的中药艾蒿。通过广泛的光谱数据和ECD / TDDFT计算分析，阐明了1-4的结构，包括其绝对构型。化合物1-4表现出细胞毒性，IC50值为7.2至23.3μM。Ca2 +在细胞质和内质网（ER）中的积累表明1通过改善ER应激介导了HT-29癌细胞的凋亡，这一点在IRE1α上调的基础上通过未折叠的蛋白反应（UPR）途径进一步证明了， p-PERK，ATF6和CHOP。