A series of amide anthraquinone derivatives, an important component of some traditional Chinese medicines, were structurally modified and the resulting antitumor activities were evaluated. The compounds showed potent anti-proliferative activities against eight human cancer cell lines, with no noticeable cytotoxicity towards normal cells. Among the candidate compounds, 1-nitro-2-acyl anthraquinone-leucine (8a) showed the greatest inhibition of HCT116 cell activity with an IC50 of 17.80 μg/mL. In addition, a correlation model was established in a three-dimensional quantitative structure-activity relationship (3D-QSAR) study using Comparative Molecular Field Analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA). Moreover, compound 8a effectively killed tumor cells by reactive oxygen species (ROS)-JNK activation, causing an increase in ROS levels, JNK phosphorylation, and mitochondrial stress. Cytochrome c was then released into cytoplasm, which, in turn activated the cysteine protease pathway and ultimately induced tumor cell apoptosis, suggesting a potential use of this compound for colon cancer treatment.

中文翻译：

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新型蒽醌化合物通过活性氧/JNK 通路抑制结肠癌细胞增殖

一系列酰胺蒽醌衍生物是一些中药的重要成分，经过结构修饰，并评估了由此产生的抗肿瘤活性。这些化合物对八种人类癌细胞系显示出有效的抗增殖活性，对正常细胞没有明显的细胞毒性。在候选化合物中，1-硝基-2-酰基蒽醌-亮氨酸 (8a) 对 HCT116 细胞活性的抑制作用最大，IC50 为 17.80 μg/mL。此外，使用比较分子场分析（CoMFA）和比较分子相似性指数分析（CoMSIA）在三维定量构效关系（3D-QSAR）研究中建立了相关模型。此外，化合物 8a 通过活性氧 (ROS)-JNK 激活有效杀死肿瘤细胞，导致 ROS 水平增加、JNK 磷酸化和线粒体应激。然后细胞色素 c 被释放到细胞质中，进而激活半胱氨酸蛋白酶途径并最终诱导肿瘤细胞凋亡，表明该化合物可能用于治疗结肠癌。