4'-dehydroxyarctigenin

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 呋喃类木脂素
• 英文名称: 4'-dehydroxyarctigenin
• 英文别名: 4-dehydroxylarctigenin；(8R,8'R)-3,3',4'-trimethoxylignano-9,9'-lactone；(3R,4R)-3-(3-methoxybenzyl)-4-(3,4-dimethoxybenzyl)dihydrofuran-2(3H)-one；(3R,4R)-4-[(3,4-dimethoxyphenyl)methyl]-3-[(3-methoxyphenyl)methyl]oxolan-2-one
• 化学式: C₂₁H₂₄O₅
• 分子量: 356.419
• InChiKey: MFUMREBAQCWFLL-FUHWJXTLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  间甲氧基苯甲醇 在 三溴化磷 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.83h， 生成 4'-dehydroxyarctigenin
  参考文献：
  名称：

  AMPA 和红藻氨酸受体拮抗剂牛蒡甙元类似物的合成和药理学表征

  摘要：

  (−)-Arctigenin 和一系列新类似物已被合成，然后使用 Ca 2+流入测定测试其作为 HEK293 细胞中表达的人同聚 GluA1 和 GluK2 受体的 AMPA 和红藻氨酸受体拮抗剂的潜力。一般来说，这些化合物对两种受体都显示出拮抗剂活性，并且对 AMPAR 的活性明显更高。 Schild 分析表明螺环类似物6c充当非竞争性拮抗剂。分子对接研究表明， 6c对接至 GluA2 四聚体的 X 射线晶体结构中，表明 (−)-牛蒡苷元及其类似物在跨膜结构域中的结合方式与已知的 AMPA 受体非竞争性拮抗剂 GYKI53655 和抗癫痫药吡仑帕奈。本文描述的牛蒡甙元衍生物可以作为开发治疗癫痫的药物的新先导物。

  DOI：

  10.1039/d1ob01653a

文献信息

• Discovery of stereospecific cytotoxicity of (8R,8′R)-trans-arctigenin against insect cells and structure-activity relationship on aromatic ring
  作者：Satoshi Yamauchi、Asuka Nishimoto、Hisashi Nishiwaki、Kosuke Nishi、Takuya Sugahara

  DOI：10.1016/j.bmcl.2020.127191

  日期：2020.7

  One of the arctigenin stereoisomers, (8R,8'R)-trans-form 1, showed stereospecific cytotoxicity against insect cells, Sf9 and NIAS-AeAl-2 cells. By the comparison with other stereoisomers, the most importance of the 8'R stereochemistry for the higher activities was clarified. On the other hand, the wider range of activity level among stereoisomers against cancer cells, HL-60, was not observed. The structure-activity relationship research using derivatives bearing (8R,8'R)-trans-form was performed to show the same level of activities of 3-iodo, 4-iodo, and 3,4-methylenedioxy derivatives 28, 29, and 36 as (8R,8'R)-trans-arctigenin 1. In the examination of thiono derivatives, 4-iodo thiono and 3,4-methylenedioxy thiono derivatives 66, 67 showed similar level of activities to that of (8R,8'R)-trans-arctigenin 1. The expression of ribosomal 28S rRNA gene of Sf9 cells was increased by (8R,8'R)-trans-arctigenin 1, whereas a degradation of DNA was not observed.
• Synthesis and cytotoxicity evaluation of 4-amino-4-dehydroxylarctigenin derivatives in glucose-starved A549 tumor cells
  作者：Min Lei、Xianwen Gan、Kun Zhao、Qiang Yu、Lihong Hu

  DOI：10.1016/j.bmcl.2014.12.061

  日期：2015.2

  The natural product arctigenin (ATG) demonstrated preferential cytotoxicity to cancer cells under glucose starvation. A series of 4-amino-4-dehydroxylarctigenin derivatives based on lead compound ATG were designed and synthesized by bioisosteric modifications. Their cytotoxicities were evaluated in glucose-starved A549 tumor cells and the results indicated that the 4-amino-4-dehydroxylarctigenin showed more potent cytotoxicity than arctigenin, and the further substituent group on 4-amino would result in the cytotoxicities decreased significantly. 4-Substituted-arctigenin could selectively target on glucose-starved A549 tumor cells which provide an alternative strategy for anticancer drug development with minimal normal tissue toxicity. (C) 2014 Elsevier Ltd. All rights reserved.
• Synthesis and pharmacological characterisation of arctigenin analogues as antagonists of AMPA and kainate receptors
  作者：Lisa-Maria Rečnik、Robert J. Thatcher、Shahida Mallah、Craig P. Butts、Graham L. Collingridge、Elek Molnár、David E. Jane、Christine L. Willis

  DOI：10.1039/d1ob01653a

  日期：——

  a non-competitive antagonist. Molecular docking studies in which 6c was docked into the X-ray crystal structure of the GluA2 tetramer suggest that (−)-arctigenin and its analogues bind in the transmembrane domain in a similar manner to the known AMPA receptor non-competitive antagonists GYKI53655 and the antiepileptic drug perampanel. The arctigenin derivatives described herein may serve as novel leads

  (−)-Arctigenin 和一系列新类似物已被合成，然后使用 Ca 2+流入测定测试其作为 HEK293 细胞中表达的人同聚 GluA1 和 GluK2 受体的 AMPA 和红藻氨酸受体拮抗剂的潜力。一般来说，这些化合物对两种受体都显示出拮抗剂活性，并且对 AMPAR 的活性明显更高。 Schild 分析表明螺环类似物6c充当非竞争性拮抗剂。分子对接研究表明， 6c对接至 GluA2 四聚体的 X 射线晶体结构中，表明 (−)-牛蒡苷元及其类似物在跨膜结构域中的结合方式与已知的 AMPA 受体非竞争性拮抗剂 GYKI53655 和抗癫痫药吡仑帕奈。本文描述的牛蒡甙元衍生物可以作为开发治疗癫痫的药物的新先导物。