(E)-3-(2,5-diethoxyphenyl)prop-2-enoic acid

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-3-(2,5-diethoxyphenyl)prop-2-enoic acid
• 化学式: C₁₃H₁₆O₄
• 分子量: 236.268
• InChiKey: JVYJEAXNJIIKNC-VMPITWQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(2,5-diethoxyphenyl)prop-2-enoic acid 在 potassium carbonate 、 三乙胺 、 三氯氧磷 作用下， 以 丙酮 为溶剂， 反应 0.33h， 生成 (E)-N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl)-3-(2,5-dimethoxyphenyl)acrylamide
  参考文献：
  名称：

  Design and synthesis of novel tranilast analogs: Docking, antiproliferative evaluation and in-silico screening of TGFβR1 inhibitors

  摘要：

  The discovery of the antiproliferative potential of tranilast prompted additional studies directed at understanding the mechanisms of tranilast action. Its inhibitory effect on cell proliferation depends principally on the capacity of tranilast to interfere with transforming growth factor beta (TGFβR1) signaling. This work summarizes design, synthesis and biological evaluation of sixteen novel tranilast analogs on different tumors such as PC-3, HepG-2 and MCF-7 cell lines. The in vitro cytotoxicity was evaluated using MTT assay showed that, twelve compounds out of sixteen showed higher cytotoxic activities (IC₅₀'s 1.1-6.29 µM), than that of the reference standard, 5-FU (IC₅₀ 7.53 µM). The promising cytotoxic hits (4b, 7a, b and 14c-e), proved to be selective to cancer cells when their cytotoxicity's are examined on human normal cell line (WI-38). Then they are investigated for their possible mode of action as TGFβR1 inhibitors; remarkable inhibition of TGFβR1 by these hits was observed at the range of IC₅₀ 0.087-3.276 μM. The cell cycle analysis of the most potent TGFβR1 inhibitor, 4b revealed cell cycle arrest at G₂/M phase on prostate cancer cells. Additionally, it is clearly indicated apoptosis induction at Pre-G1 phase, this is substantiated by significant increase in the expression on the tumor suppressor gene, p53 and up regulation the level of apoptosis mediator, caspase-3. In addition, in silico study was performed for validating the physicochemical and ADME properties which revealed that, all compounds are orally bioavailable with no side effects complying with Lipinski rule. The proposed mode of action can be further explored on the light of molecular modeling simulation of the most potent compounds, 4b and 14e which were docked into the active sites of TGFβR1 to predict their affinities toward the receptor.

  DOI：

  10.1016/j.bioorg.2020.104368
• 作为产物：
  描述：

  丙二酸 、 2,5-二乙氧基苯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 (E)-3-(2,5-diethoxyphenyl)prop-2-enoic acid
  参考文献：
  名称：

  Design and synthesis of novel tranilast analogs: Docking, antiproliferative evaluation and in-silico screening of TGFβR1 inhibitors

  摘要：

  The discovery of the antiproliferative potential of tranilast prompted additional studies directed at understanding the mechanisms of tranilast action. Its inhibitory effect on cell proliferation depends principally on the capacity of tranilast to interfere with transforming growth factor beta (TGFβR1) signaling. This work summarizes design, synthesis and biological evaluation of sixteen novel tranilast analogs on different tumors such as PC-3, HepG-2 and MCF-7 cell lines. The in vitro cytotoxicity was evaluated using MTT assay showed that, twelve compounds out of sixteen showed higher cytotoxic activities (IC₅₀'s 1.1-6.29 µM), than that of the reference standard, 5-FU (IC₅₀ 7.53 µM). The promising cytotoxic hits (4b, 7a, b and 14c-e), proved to be selective to cancer cells when their cytotoxicity's are examined on human normal cell line (WI-38). Then they are investigated for their possible mode of action as TGFβR1 inhibitors; remarkable inhibition of TGFβR1 by these hits was observed at the range of IC₅₀ 0.087-3.276 μM. The cell cycle analysis of the most potent TGFβR1 inhibitor, 4b revealed cell cycle arrest at G₂/M phase on prostate cancer cells. Additionally, it is clearly indicated apoptosis induction at Pre-G1 phase, this is substantiated by significant increase in the expression on the tumor suppressor gene, p53 and up regulation the level of apoptosis mediator, caspase-3. In addition, in silico study was performed for validating the physicochemical and ADME properties which revealed that, all compounds are orally bioavailable with no side effects complying with Lipinski rule. The proposed mode of action can be further explored on the light of molecular modeling simulation of the most potent compounds, 4b and 14e which were docked into the active sites of TGFβR1 to predict their affinities toward the receptor.

  DOI：

  10.1016/j.bioorg.2020.104368

文献信息

• Design and synthesis of novel tranilast analogs: Docking, antiproliferative evaluation and in-silico screening of TGFβR1 inhibitors
  作者：Magda M.F. Ismail、Heba S.A. El-Zahabi、Rabab S. Ibrahim、Ahmed B.M. Mehany

  DOI：10.1016/j.bioorg.2020.104368

  日期：2020.12

  The discovery of the antiproliferative potential of tranilast prompted additional studies directed at understanding the mechanisms of tranilast action. Its inhibitory effect on cell proliferation depends principally on the capacity of tranilast to interfere with transforming growth factor beta (TGFβR1) signaling. This work summarizes design, synthesis and biological evaluation of sixteen novel tranilast analogs on different tumors such as PC-3, HepG-2 and MCF-7 cell lines. The in vitro cytotoxicity was evaluated using MTT assay showed that, twelve compounds out of sixteen showed higher cytotoxic activities (IC₅₀'s 1.1-6.29 µM), than that of the reference standard, 5-FU (IC₅₀ 7.53 µM). The promising cytotoxic hits (4b, 7a, b and 14c-e), proved to be selective to cancer cells when their cytotoxicity's are examined on human normal cell line (WI-38). Then they are investigated for their possible mode of action as TGFβR1 inhibitors; remarkable inhibition of TGFβR1 by these hits was observed at the range of IC₅₀ 0.087-3.276 μM. The cell cycle analysis of the most potent TGFβR1 inhibitor, 4b revealed cell cycle arrest at G₂/M phase on prostate cancer cells. Additionally, it is clearly indicated apoptosis induction at Pre-G1 phase, this is substantiated by significant increase in the expression on the tumor suppressor gene, p53 and up regulation the level of apoptosis mediator, caspase-3. In addition, in silico study was performed for validating the physicochemical and ADME properties which revealed that, all compounds are orally bioavailable with no side effects complying with Lipinski rule. The proposed mode of action can be further explored on the light of molecular modeling simulation of the most potent compounds, 4b and 14e which were docked into the active sites of TGFβR1 to predict their affinities toward the receptor.