3-chloro-4-methyl-7-((10S)-dihydroartemisin-10-oxy)-2H-1-chromen-2-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: 3-chloro-4-methyl-7-((10S)-dihydroartemisin-10-oxy)-2H-1-chromen-2-one
• 英文别名: 3-chloro-4-methyl-7-[[(1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.04,13.08,13]hexadecan-10-yl]oxy]chromen-2-one
• 化学式: C₂₅H₂₉ClO₇
• 分子量: 476.954
• InChiKey: YXZFPPUTDXKBSW-CBTOJQLJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  33
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  间苯二酚 在 硫酸 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.17h， 生成 3-chloro-4-methyl-7-((10S)-dihydroartemisin-10-oxy)-2H-1-chromen-2-one
  参考文献：
  名称：

  Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents

  摘要：

  To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G(0)/G(1) phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.04.005

文献信息

• 青蒿素-香豆素杂合分子及其制备方法和应用
  申请人：沈阳药科大学

  公开号：CN106188088B

  公开（公告）日：2019-03-01

  本发明的目的是提供一种青蒿素‑香豆素杂合分子及其制备方法和用途，提供一种其在药学上可接受的盐、溶剂化物、光学异构体或多晶型物，还提供一种以该衍生物或其盐为活性成分的药物。本发明所涉及的化合物结构式如式（I）或其药学上可接受的盐、溶剂化物、光学异构体或多晶型物：其中，L=O,O(CH2)nO，n=0～3，R1，R2独立地为氢原子，卤素，羟基，C1～C10羧基，C1～C10酯基，氰基，硝基，C1～C10烷基，C1～C10烷氧基，C3～C7环烷基，卤代的C1～C10烷基、C1～C10烷氧基。（I）。
• Design, synthesis, cytotoxicity and mechanism of novel dihydroartemisinin-coumarin hybrids as potential anti-cancer agents
  作者：Haonan Yu、Zhuang Hou、Ye Tian、Yanhua Mou、Chun Guo

  DOI：10.1016/j.ejmech.2018.04.005

  日期：2018.5

  To develop novel agents with anticancer activities, thirty-four new dihydroartemisinin-coumarin hybrids were designed and synthesized in this study. Those compounds were identified that had great anticancer activity against two cancer cell lines (MDA-MB-231 and HT-29). The structure-activity relationships of the derivatives were also discussed, and the results of docking analysis had shown that carbonic anhydrases IX (CA IX) was very likely to be one of the drug targets of the hybrids. Meanwhile, to clarify the mechanism of the anticancer activity of the hybrids molecule, we did further exploration in the bioactivity of the hybrids. The results had shown that these derivatives obviously inhibited proliferation of HT-29 cell lines, arrested G(0)/G(1) phase of HT-29 cells, suppressed the migration of tumor cells, and induced a great decrease in mitochondrial membrane potential leading to apoptosis of cancer cells. Interestingly, the hybrids also induced the other cell death pathway-ferroptosis. (C) 2018 Elsevier Masson SAS. All rights reserved.