8α-tigloyloxy-hirsutinolide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 8α-tigloyloxy-hirsutinolide
• 英文别名: 8α-tigloyloxyhirsutinolide；Rel-8Alpha-Tigloyloxyhirsutinolide；[(1R,2E,8S,10R,11S)-11-hydroxy-6-(hydroxymethyl)-1,10-dimethyl-5-oxo-4,14-dioxatricyclo[9.2.1.03,7]tetradeca-2,6-dien-8-yl] (E)-2-methylbut-2-enoate
• 化学式: C₂₀H₂₆O₇
• 分子量: 378.422
• InChiKey: TVCSPTBQHQMYOG-BFWKSYKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8α-tigloyloxy-hirsutinolide 、 惕格酸 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以40%的产率得到(4S,6R,E)-7-hydroxy-6,10-dimethyl-3-((((E)-2-methylbut-2-enoyl)oxy)methyl)-2-oxo-2,4,5,6,7,8,9,10-octahydro-7,10-epoxycyclodeca[b]furan-4-yl (E)-2-methylbut-2-enoate
  参考文献：
  名称：

  Hirsutinolide Series Inhibit Stat3 Activity, Alter GCN1, MAP1B, Hsp105, G6PD, Vimentin, TrxR1, and Importin α-2 Expression, and Induce Antitumor Effects against Human Glioma

  摘要：

  We report that hirsutinolide series, 6, 7, 10, 11, 20, and 22, and the semisynthetic analogues, 30, 31, 33, and 36, inhibit constitutively active signal transducer and activator of transcription (Stat)3 and malignant glioma phenotype. A position 13 lipophilic ester group is required for activity. Molecular modeling and nuclear magnetic resonance structural analyses reveal direct hirsutinolide:Stat3 binding. One-hour treatment of cells with 6 and 22 also upregulated importin subunit alpha-2 levels and repressed translational activator GCN1, microtubule-associated protein (MAP) 1B, thioredoxin reductase (TrxR) 1 cytoplasmic isoform 3, glucose-6-phosphate 1-dehydrogenase isoform a, Hsp105, vimentin, and tumor necrosis factor a-induced protein (TNAP)2 expression. Active hirsutinolides inhibited anchorage-dependent and three-dimensional spheroid growth, survival, and migration of human glioma lines and glioma patients' tumor-derived xenograft cells harboring constitutively active Stat3. Oral gavage delivery of 6 or 22 inhibited human glioma tumor growth in subcutaneous mouse xenografts. The inhibition of Stat3 signaling represents part of the hirsutinolide-mediated mechanisms to induce antitumor effects.

  DOI：

  10.1021/acs.jmedchem.5b00686

文献信息

• Hirsutinolide Series Inhibit Stat3 Activity, Alter GCN1, MAP1B, Hsp105, G6PD, Vimentin, TrxR1, and Importin α-2 Expression, and Induce Antitumor Effects against Human Glioma
  作者：Gabriella Miklossy、Ui Joung Youn、Peibin Yue、Mingming Zhang、Chih-Hong Chen、Tyvette S. Hilliard、David Paladino、Yifei Li、Justin Choi、Jann N. Sarkaria、Joel K. Kawakami、Supakit Wongwiwatthananukit、Yuan Chen、Dianqing Sun、Leng Chee Chang、James Turkson

  DOI：10.1021/acs.jmedchem.5b00686

  日期：2015.10.8

  We report that hirsutinolide series, 6, 7, 10, 11, 20, and 22, and the semisynthetic analogues, 30, 31, 33, and 36, inhibit constitutively active signal transducer and activator of transcription (Stat)3 and malignant glioma phenotype. A position 13 lipophilic ester group is required for activity. Molecular modeling and nuclear magnetic resonance structural analyses reveal direct hirsutinolide:Stat3 binding. One-hour treatment of cells with 6 and 22 also upregulated importin subunit alpha-2 levels and repressed translational activator GCN1, microtubule-associated protein (MAP) 1B, thioredoxin reductase (TrxR) 1 cytoplasmic isoform 3, glucose-6-phosphate 1-dehydrogenase isoform a, Hsp105, vimentin, and tumor necrosis factor a-induced protein (TNAP)2 expression. Active hirsutinolides inhibited anchorage-dependent and three-dimensional spheroid growth, survival, and migration of human glioma lines and glioma patients' tumor-derived xenograft cells harboring constitutively active Stat3. Oral gavage delivery of 6 or 22 inhibited human glioma tumor growth in subcutaneous mouse xenografts. The inhibition of Stat3 signaling represents part of the hirsutinolide-mediated mechanisms to induce antitumor effects.