Z-K8 (2), the racemic form of isochaihulactone (1), previously showed significant antitumor effects in A549 and LNCaP tumor-bearing mice. In the present study, 17 derivatives of 2 were designed, synthesized and evaluated for their anti-proliferative activity against four human tumor cell lines. All new derivatives exhibited high potency against A549 and P-glycoprotein (P-gp)-overexpressing KB-VIN. One of our new derivatives exhibited greater activity against three tested tumor cells (A549, KB, and KB-VIN) than 2, and induced cell cycle arrest in the G₂/M phase. Moreover, SAR conclusions were first established for this series of compounds. Our study clearly identified a structural feature that should be retained for good activity and also a moiety that can tolerate various modifications and, thus, is ideal for further changes.

中文翻译：

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(±)-异柴胡内酯衍生物的设计、合成及构效关系

Z-K8 ( 2 ) 是异柴胡内酯 ( 1 )的外消旋形式，之前在 A549 和 LNCaP 荷瘤小鼠中显示出显着的抗肿瘤作用。在本研究中，设计、合成了2的 17 种衍生物，并评估了它们对四种人类肿瘤细胞系的抗增殖活性。所有新的衍生物都表现出对 A549 和 P-糖蛋白 (P-gp) 过表达的 KB-VIN 的高效力。我们的一种新衍生物对三种测试的肿瘤细胞（A549、KB 和 KB-VIN）表现出比2更强的活性，并在 G ₂中诱导细胞周期停滞/M相。此外，首先建立了该系列化合物的SAR结论。我们的研究清楚地确定了一个结构特征应该保留以获得良好的活性，以及​​一个可以耐受各种修饰的部分，因此是进一步改变的理想选择。