1-hydroxy-3-(oxiran-2-ylmethoxy)-10H-acridin-9-one | 1202024-64-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 1-hydroxy-3-(oxiran-2-ylmethoxy)-10H-acridin-9-one
• CAS: 1202024-64-3
• 化学式: C₁₆H₁₃NO₄
• 分子量: 283.284
• InChiKey: ZDFSKOYYYDHYCC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  71.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1,3-二羟基-9(10H)-吖啶酮 、 环氧氯丙烷 在 caesium carbonate 作用下， 以 丙酮 为溶剂， 以13.1%的产率得到1-hydroxy-3-(oxiran-2-ylmethoxy)-10H-acridin-9-one
  参考文献：
  名称：

  Oxiranylmethyloxy or thiiranylmethyloxy-azaxanthones and -acridone analogues as potential topoisomerase I inhibitors

  摘要：

  A total of seven new oxyranylmethyloxy or thiiranylmethyloxy group substituted 5-azaxanthones and -acridones analogues were synthesized and tested for their biological activities for cancer cell lines and topoisomerases. Among the compounds, compound 5, 3-thiiranylmethyloxy-1-hydroxy-5-azaxanthone, showed effective topoisomerase I inhibitory activity, 50% and 27% inhibition ratio at 100 and 20 mu M, respectively. This result is the first finding of the function of 5-azaxanthone compounds for topoisomerase I inhibition and can provide a novel skeleton for the anticancer drug development process. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.09.091

文献信息

• MHY440, a Novel Topoisomerase Ι Inhibitor, Induces Cell Cycle Arrest and Apoptosis via a ROS-Dependent DNA Damage Signaling Pathway in AGS Human Gastric Cancer Cells
  作者：Jung Jang、Yong Kang、Bokyung Sung、Min Kim、Chaeun Park、Dongwan Kang、Hyung Moon、Hae Chung、Nam Kim

  DOI：10.3390/molecules24010096

  日期：——

  apoptotic effect of MHY440 was reactive oxygen species (ROS)-dependent, as evidenced by the inhibition of MHY440-induced PARP cleavage and ROS generation via N-acetylcysteine-induced ROS scavenging. Taken together, MHY440 showed anticancer effects by inhibiting Topo I, regulating the cell cycle, inducing apoptosis through caspase activation, and generating ROS, suggesting that MHY440 has considerable potential

  我们研究了MHY440在AGS人胃癌细胞中的抗肿瘤活性和作用机理。MHY440抑制拓扑异构酶（Topo）I活性，并与DNA损伤应答信号传导途径相关。相对于Hs27人包皮成纤维细胞，它对AGS细胞表现出更强的抗增殖作用，并且这种作用是时间和浓度依赖性的。MHY440还可以通过减少细胞周期蛋白B1，Cdc2和Cdc25c并上调p53和p73来增加G2 / M期的细胞停滞。MHY440通过上调Fas-L，Fas和Bax以及BH3相互作用域死亡激动剂和聚（ADP-核糖）聚合酶的蛋白水解诱导AGS细胞凋亡。它也导致线粒体膜电位的丧失。Z-VAD-FMK预处理可抑制MHY440诱导的凋亡细胞死亡，泛半胱天冬酶抑制剂，表明凋亡是caspase依赖性的。此外，MHY440的凋亡效应是活性氧（ROS）依赖性的，这可以通过抑制MHY440诱导的PARP裂解和通过N-乙酰半胱氨酸诱导的ROS清除产生ROS来证明
• Oxiranylmethyloxy or thiiranylmethyloxy-azaxanthones and -acridone analogues as potential topoisomerase I inhibitors
  作者：Hee-Ju Cho、Mi-Ja Jung、Youngjoo Kwon、Younghwa Na

  DOI：10.1016/j.bmcl.2009.09.091

  日期：2009.12

  A total of seven new oxyranylmethyloxy or thiiranylmethyloxy group substituted 5-azaxanthones and -acridones analogues were synthesized and tested for their biological activities for cancer cell lines and topoisomerases. Among the compounds, compound 5, 3-thiiranylmethyloxy-1-hydroxy-5-azaxanthone, showed effective topoisomerase I inhibitory activity, 50% and 27% inhibition ratio at 100 and 20 mu M, respectively. This result is the first finding of the function of 5-azaxanthone compounds for topoisomerase I inhibition and can provide a novel skeleton for the anticancer drug development process. (C) 2009 Elsevier Ltd. All rights reserved.