Key Laboratory for Chemical Biology and Molecular Engineering of Ministry of Education, Institute of Biotechnology, Shanxi University, Taiyuan 030006, China.
Molecules. 2020 Apr 4;25(7):1672. doi: 10.3390/molecules25071672.
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 () showed the greatest inhibition of HCT116 cell activity with an IC 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 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.
一系列酰胺蒽醌衍生物是一些中药的重要组成部分，我们对其进行了结构修饰，并评估了其抗肿瘤活性。这些化合物对八种人癌细胞系具有很强的增殖抑制活性，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（）对 HCT116 细胞活性的抑制作用最强，IC 为 17.80 μg/mL。此外，通过比较分子场分析（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，化合物通过活性氧（ROS）-JNK 激活有效杀死肿瘤细胞，导致 ROS 水平升高、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，这反过来又激活了半胱氨酸蛋白酶途径，最终诱导肿瘤细胞凋亡，这表明该化合物在结肠癌治疗方面有一定的应用潜力。
