(E)-3-[3-(tert-butyl-dimethyl-silanyloxy)-4-methoxyphenyl]-1-(3,4,5-trimethoxy-phenyl)-prop-2-en-1-one | 537937-67-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-3-[3-(tert-butyl-dimethyl-silanyloxy)-4-methoxyphenyl]-1-(3,4,5-trimethoxy-phenyl)-prop-2-en-1-one
• 英文别名: E-3-(3-tert-butyldimethylsilyloxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)propenone；(E)-3-[3-[tert-butyl(dimethyl)silyl]oxy-4-methoxyphenyl]-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 537937-67-0
• 化学式: C₂₅H₃₄O₆Si
• 分子量: 458.627
• InChiKey: DRZOZEPKTUOZNC-ZRDIBKRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.0
• 重原子数：
  32
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  63.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-3-[3-(tert-butyl-dimethyl-silanyloxy)-4-methoxyphenyl]-1-(3,4,5-trimethoxy-phenyl)-prop-2-en-1-one 在 盐酸 作用下， 以 甲醇 为溶剂， 生成 (E)-3-(3-hydroxy-4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Microtubule inhibitors containing immunostimulatory agents promote cancer immunochemotherapy by inhibiting tubulin polymerization and tryptophan-2,3-dioxygenase

  摘要：

  A combination therapeutic regimen via introducing tryptophan 2,3-dioxygenase inhibitors into microtubule inhibitors was performed and evaluated for their antitumor activity. Thereinto, HT2, composed of combretastatin A-4 (CA-4) and tryptophan-2,3-dioxygenase (TDO) inhibitor by a linker, displayed the most potent activity with 10-fold higher than its parent CA-4 against HepG2, A549 and HCT-116 cancer cell lines. Mechanism studies suggested that HT2 inhibited tubulin polymerization and cell migration, caused G2 phase arrest, induced apoptosis by mitochondrial mediated apoptotic pathway, concurrent depolarized the mitochondria membrane potentials and caused reactive oxygen species (ROS) production in HepG2 cells. Moreover, HT2 could enhance T-cell immune responses in vitro by releasing a TDO inhibitor to suppress TDO expression and blockade kynurenine production. As expected, HT2 could remarkably promote the antitumor activity of CA-4 in either immunocompetent H22 or immunodeficient A549 tumor xenograft models without observable toxic effects. More importantly, HT2 increased the level of splenic and tumor-infiltrated T cells and in turn effectively boosted the inhibition effect in H22 xenografted tumor growth. Collectively, this immunochemotherapeutic strategy can be applied to promote chemotherapeutic effect. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111949
• 作为产物：
  描述：

  3',4',5'-三甲氧基苯乙酮 、 3-叔-丁基二甲基硅氧基-4-甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (E)-3-[3-(tert-butyl-dimethyl-silanyloxy)-4-methoxyphenyl]-1-(3,4,5-trimethoxy-phenyl)-prop-2-en-1-one
  参考文献：
  名称：

  Microtubule inhibitors containing immunostimulatory agents promote cancer immunochemotherapy by inhibiting tubulin polymerization and tryptophan-2,3-dioxygenase

  摘要：

  A combination therapeutic regimen via introducing tryptophan 2,3-dioxygenase inhibitors into microtubule inhibitors was performed and evaluated for their antitumor activity. Thereinto, HT2, composed of combretastatin A-4 (CA-4) and tryptophan-2,3-dioxygenase (TDO) inhibitor by a linker, displayed the most potent activity with 10-fold higher than its parent CA-4 against HepG2, A549 and HCT-116 cancer cell lines. Mechanism studies suggested that HT2 inhibited tubulin polymerization and cell migration, caused G2 phase arrest, induced apoptosis by mitochondrial mediated apoptotic pathway, concurrent depolarized the mitochondria membrane potentials and caused reactive oxygen species (ROS) production in HepG2 cells. Moreover, HT2 could enhance T-cell immune responses in vitro by releasing a TDO inhibitor to suppress TDO expression and blockade kynurenine production. As expected, HT2 could remarkably promote the antitumor activity of CA-4 in either immunocompetent H22 or immunodeficient A549 tumor xenograft models without observable toxic effects. More importantly, HT2 increased the level of splenic and tumor-infiltrated T cells and in turn effectively boosted the inhibition effect in H22 xenografted tumor growth. Collectively, this immunochemotherapeutic strategy can be applied to promote chemotherapeutic effect. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111949

文献信息

• Substituted arylcycloalkanes, compositions containing them and use thereof
  申请人：——

  公开号：US20030149072A1

  公开（公告）日：2003-08-07

  Substituted arylcycloalkanes, compositions containing them and use thereof. The present invention relates especially to substituted arylcycloalkanes with therapeutic activity, which may be used such as in oncology.

  被取代的芳基环烷烃、含有它们的组合物及其使用。本发明特别涉及具有治疗活性的取代芳基环烷烃，可用于肿瘤学等领域。
• Combretastatin-like chalcones as inhibitors of microtubule polymerisation. Part 2: Structure-based discovery of alpha-aryl chalcones
  作者：Sylvie Ducki、Grant Mackenzie、Ben Greedy、Simon Armitage、Jérémie Fournier Dit Chabert、Elizabeth Bennett、Jim Nettles、James P. Snyder、Nicholas J. Lawrence

  DOI：10.1016/j.bmc.2009.09.044

  日期：2009.11

  Tubulin is an important molecular target in cancer chemotherapy. Antimitotic agents able to bind to the protein are currently under study, commonly used in the clinic to treat a variety of cancers and/or exploited as probes to investigate the protein's structure and function. Here we report the binding modes for a series of colchicinoids, combretastatin A4 and chalcones established from docking studies carried out on the structure of tubulin in complex with colchicine. The proposed models, in agreement with published biochemical data, show that combretastatin A4 binds to the colchicine site of beta-tubulin and that chalcones assume an orientation similar to that of podophyllotoxin. The models can be used to design a new class of podophyllotoxin mimics, the alpha-aryl chalcones, capable of binding to the colchicine-binding site of beta-tubulin with higher affinity. (C) 2009 Elsevier Ltd. All rights reserved.
• Microtubule inhibitors containing immunostimulatory agents promote cancer immunochemotherapy by inhibiting tubulin polymerization and tryptophan-2,3-dioxygenase
  作者：Shixian Hua、Feihong Chen、Shaohua Gou

  DOI：10.1016/j.ejmech.2019.111949

  日期：2020.2

  A combination therapeutic regimen via introducing tryptophan 2,3-dioxygenase inhibitors into microtubule inhibitors was performed and evaluated for their antitumor activity. Thereinto, HT2, composed of combretastatin A-4 (CA-4) and tryptophan-2,3-dioxygenase (TDO) inhibitor by a linker, displayed the most potent activity with 10-fold higher than its parent CA-4 against HepG2, A549 and HCT-116 cancer cell lines. Mechanism studies suggested that HT2 inhibited tubulin polymerization and cell migration, caused G2 phase arrest, induced apoptosis by mitochondrial mediated apoptotic pathway, concurrent depolarized the mitochondria membrane potentials and caused reactive oxygen species (ROS) production in HepG2 cells. Moreover, HT2 could enhance T-cell immune responses in vitro by releasing a TDO inhibitor to suppress TDO expression and blockade kynurenine production. As expected, HT2 could remarkably promote the antitumor activity of CA-4 in either immunocompetent H22 or immunodeficient A549 tumor xenograft models without observable toxic effects. More importantly, HT2 increased the level of splenic and tumor-infiltrated T cells and in turn effectively boosted the inhibition effect in H22 xenografted tumor growth. Collectively, this immunochemotherapeutic strategy can be applied to promote chemotherapeutic effect. (C) 2019 Elsevier Masson SAS. All rights reserved.