The core of solid tumors is characterized by hypoxia and a nutrient-starved microenvironment and has gained much attention as targets of anti-cancer drugs. In the course of search for selective growth inhibitors against the cancer cells adapted to nutrient starvation, epidithiodiketopiperazine DC1149B (1) together with structurally related compounds, trichodermamide A (2) and aspergillazine A (3), were isolated from culture extract of marine-derived Trichoderma lixii. Compounds 1 exhibited potent selective cytotoxic activity against human pancreatic carcinoma PANC-1 cells cultured under glucose-starved conditions with IC₅₀ values of 0.02 µM. The selective index of the compound 1 was found to be 35,500-fold higher for cells cultured under glucose-starved conditions than those under the general culture conditions. The mechanistic analysis indicated that compound 1 inhibited the response of the ER stress signaling. In addition, these effects of compound 1 could be mediated by inhibiting complex II in the mitochondrial electron transport chain.

中文翻译：

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由海洋衍生的 Trichoderma lixii 产生的桥二硫二酮哌嗪 DC1149B 对适应葡萄糖饥饿的癌细胞的选择性细胞毒性。

实体瘤的核心以缺氧和营养匮乏的微环境为特征，作为抗癌药物的靶点备受关注。在寻找针对适应营养饥饿的癌细胞的选择性生长抑制剂的过程中，桥二硫二酮哌嗪 DC1149B ( 1 ) 以及结构相关的化合物木霉酰胺 A ( 2 ) 和曲霉嗪A ( 3 ) 是从海洋来源的培养提取物中分离出来的。木霉。化合物1对在葡萄糖饥饿条件下培养的人胰腺癌 PANC-1 细胞表现出有效的选择性细胞毒活性，IC ₅₀值为 0.02 µM。化合物的选择性指数1被发现是35,500倍为比一般培养条件下葡萄糖饥饿条件下培养的细胞中更高。机理分析表明，化合物1抑制了内质网应激信号的反应。此外，化合物1 的这些作用可以通过抑制线粒体电子传递链中的复合物 II 来介导。