α-2-deoxydihydroartemisinin | 94668-17-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氧吡喃
• 英文名称: α-2-deoxydihydroartemisinin
• 英文别名: (3R,3a1R,6R,6aS,9S,10aR)-3,6,9-trimethyldecahydro-10aH-3a1,9-epoxyoxepino[4,3,2-ij]isochromen-2-ol；(1S,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15-trioxatetracyclo[10.2.1.04,13.08,13]pentadecan-10-ol
• CAS: 94668-17-4
• 化学式: C₁₅H₂₄O₄
• 分子量: 268.353
• InChiKey: JQGOBHOUYKYFPD-KDTBHNEXSA-N

物化性质

• 沸点：
  369.9±42.0 °C(Predicted)
• 密度：
  1.21±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  47.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  双氢青蒿素 在 palladium 10% on activated carbon 、 氢气 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以44%的产率得到α-2-deoxydihydroartemisinin
  参考文献：
  名称：

  Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin

  摘要：

  Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycinresistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI(50) = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer. (C) 2017 Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2017.10.023

文献信息

• Structure-activity relationship study of dihydroartemisinin C-10 hemiacetal derivatives as Toll-like receptor 4 antagonists
  作者：Shuo Wang、Hongshuang Wang、Cong Lin、Tianshu Zhang、Jingwei Gao、Siru Wu、Yibo Wang、Hongyuan Li、Weihong Min、Chunlei Liu、Xiaohui Wang

  DOI：10.1016/j.bioorg.2021.105107

  日期：2021.9

  recently been discovered as a Toll-like Receptor 4 (TLR4) antagonist. However, the TLR4 antagonistic activity of DHA is modest and it exhibits cellular toxicity. In this work, the structure-activity relationship (SAR) of DHA as TLR4 antagonist was explored. Since destroying the sesquiterpene endoperoxide scaffold substantially compromised the TLR4 antagonistic activity and molecular dynamics analysis

  双氢青蒿素(DHA)，一种从传统中草药青蒿中分离出来的天然产物作为一种抗疟疾感染的临床一线药物，最近被发现是一种 Toll 样受体 4 (TLR4) 拮抗剂。然而，DHA 的 TLR4 拮抗活性是适度的，并且表现出细胞毒性。在这项工作中，探索了 DHA 作为 TLR4 拮抗剂的构效关系 (SAR)。由于破坏倍半萜内过氧化物支架显着损害了 TLR4 拮抗活性，分子动力学分析表明 C-10 羟基与髓细胞分化因子 2 (MD2) 的 E72 形成氢键以防止其深入 MD2，因此 DHA 的 SAR 为专注于 C-10 半缩醛位置。随着在 C10 位置延长直链烷烃链的长度，DHA 类似物的 TLR4 拮抗活性先增加后降低，最好的 TLR4 拮抗作用发生在 3-4 个碳的碳链长度处。相比之下，DHA 类似物的细胞毒性随着线性烷烃链长度的增加而增加。以取代卤素为末端官能团的DHA衍生物的TLR4拮抗活性
• Synthesis, anticancer evaluation and pharmacokinetic study of novel 10-O-phenyl ethers of dihydroartemisinin
  作者：Shenglin Luan、Hang Zhong、Xuan Zhao、Jinyu Yang、Yongkui Jing、Dan Liu、Linxiang Zhao

  DOI：10.1016/j.ejmech.2017.10.023

  日期：2017.12

  Twenty hybrid compounds, tethering dihydroartemisinin (DHA) with diaryl-pyrazoline/diaryl-pyrazole through ether linkage, were synthesized based on hybridization strategy and assessed for their anticancer activity. The representative compound 6f exhibited significantly elevated antiproliferative activity compared with DHA against a panel of cancer cell lines. Unexpected sensitivity of 6f in Adriamycinresistant MCF-7 cells (MCF-7/Adr) inspired subsequent research on anticancer activity of these DHA derivatives against breast cancer cell lines. All the novel compounds exhibited potent activity in three breast cancer cells including MDA-MB-231, MCF-7 and MCF-7/Adr. Most of them exerted almost 10-fold higher potency in MCF-7/Adr than in MCF-7 and MDA-MB-231 cells. Compound 5f, the most potent compound against MCF-7/Adr (GI(50) = 18 nM), was used for mechanism research which revealed that compound 5f arrested MCF-7 and MCF-7/Adr cells in G0/G1 phase with decreased levels of cyclin D1 and increased levels of p27. Preliminary pharmacokinetic properties of 5f and 6f were investigated in rats after a single intravenous administration. The high sensitivity of MCF-7/Adr indicates that these compounds have potential to be developed as therapeutic agents to treat drug-resistant cancer. (C) 2017 Published by Elsevier Masson SAS.