3-(p-tolyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one | 900145-33-7

• 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: 3-(p-tolyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 英文别名: 3-(4-methylphenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 900145-33-7
• 化学式: C₁₉H₂₀O₄
• 分子量: 312.365
• InChiKey: NEDQPDRAKGPDTL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.92
• 重原子数：
  23.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  44.76
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(p-tolyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 在 叔丁基过氧化氢 、 苄基三甲基氢氧化铵 作用下， 以 甲醇 为溶剂， 以83%的产率得到(2RS,3SR)-2,3-epoxy-3-(4-methylphenyl)-1-(3,4,5-trimethoxyphenyl)propan-1-one
  参考文献：
  名称：

  Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity

  摘要：

  The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC50 0.21 nM; combretastatin A4 CA4, IC50 2.0 nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC50 0.46 mu M; CA4, 0.10 mu M) and compete with [H-3] colchicine for binding to tubulin (8% [H-3] colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.09.039
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲醛 、 对甲基苯乙酮 在 硫酸 、 溶剂黄146 作用下， 反应 3.0h， 生成 3-(p-tolyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  Anti-proliferative potential of triphenyl substituted pyrimidines against MDA-MB-231, HCT-116 and HT-29 cancer cell lines

  摘要：

  A series of triphenyl substituted pyrimidines as analogous of colchicine and combretastatin A-4 was synthesized and evaluated for the antiproliferative potential. The compounds were screened against MDA-MB-231, HCT-116 and HT-29 cell lines using MTT assay. Most of the compounds displayed antiproliferative activity in low to sub micro molar concentration. Amongst the synthesized derivatives, compounds HK-2, HK-10 and HK-13 were found to be effective against all the three cancer cell lines. HK-2 exhibited IC50 values of 3.39 mu M, 4.78 mu M and 4.23 mu M, HK-10 showed IC50 values of 0.81 mu M, 5.89 mu M, 4.96 mu M and HK-13 showed IC50 values 3.24 mu M, 4.93 mu M and 4.73 mu M against MDA-MB-231, HCT-116 and HT-29 cancer cell lines, respectively. HK-10 was found to be the most potent compound in the series with IC50 values of 0.81 mu M against MDA-MB-231. In the cell cycle analysis, HK-2 and HK-10 showed cell arrest at G2/M phase of the cell cycle while HK-13 inhibited cell growth at the G1/G0 phase. All the three compounds showed cell death induced through apoptosis. In the docking studies, HK-2, HK-10 and HK-13 were found to fit well in the colchicine binding site of the tubulin. Some of the compounds in the current series were found to be promising against all the three cancer cell lines and may act as potent leads for further development.

  DOI：

  10.1016/j.bmcl.2020.127468

文献信息

• Modified pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as EGFRWT and EGFRT790M inhibitors: Design, synthesis, and anti-cancer evaluation
  作者：Eman S. Nossier、Rania A. Alasfoury、Mohamed Hagras、May El-Manawaty、Sara M. Sayed、Ibrahim M. Ibrahim、Hazem Elkady、Ibrahim H. Eissa、Heba S.A. Elzahabi

  DOI：10.1016/j.molstruc.2022.133971

  日期：2022.12

  This study reports design and synthesis of thirteen pyrido[2,3-d]pyrimidin-4(3H)-one derivatives as EGFR inhibitors. The antiproliferation activities were tested for all compounds against A-549, PC-3, HCT-116, and MCF-7 cell lines using doxorubicin as a reference. Compounds 6a, 6b, 7a, and 7b, which displayed the highest inhibitory percentage against all cell lines, were selected for further IC50 screening

  本研究报告了作为 EGFR 抑制剂的 13 种 pyrido[2,3 - d ]pyrimidin-4(3 H )-one 衍生物的设计和合成。使用多柔比星作为参考，测试了所有化合物对 A-549、PC-3、HCT-116 和 MCF-7 细胞系的抗增殖活性。选择对所有细胞系显示最高抑制百分比的化合物6a、6b、7a和7b用于使用厄洛替尼作为参考的进一步IC 50筛选。接下来，进一步研究了四种化合物（6a、6b、7a和7b）的野生 EGFR WT和突变 EGFR T790M抑制活性。化合物7a与参考药物厄洛替尼（IC 50  = 0.051 和 0.094 µM）相比，对 EGFR WT和 EGFR T790M显示出显着的抑制活性，IC 50值分别为 0.029 和 0.055 µM 。进一步的机制研究表明，化合物7a能够在前 G1 期和 S 期阻止细胞周期，并将总细胞凋亡提高 21.82
• 3-Aroyl-1,4-diarylpyrroles Inhibit Chronic Myeloid Leukemia Cell Growth through an Interaction with Tubulin
  作者：Giuseppe La Regina、Ruoli Bai、Antonio Coluccia、Valeria Famiglini、Sara Passacantilli、Valentina Naccarato、Giorgio Ortar、Carmela Mazzoccoli、Vitalba Ruggieri、Francesca Agriesti、Claudia Piccoli、Tiziana Tataranni、Marianna Nalli、Andrea Brancale、Stefania Vultaggio、Ciro Mercurio、Mario Varasi、Concetta Saponaro、Sara Sergio、Michele Maffia、Addolorata Maria Luce Coluccia、Ernest Hamel、Romano Silvestri

  DOI：10.1021/acsmedchemlett.7b00022

  日期：2017.5.11

  We designed 3-aroyl-1,4-diarylpyrrole (ARDAP) derivatives as potential anticancer agents having different substituents at the 1- or 4 -phenyl ring. ARDAP compounds exhibited potent inhibition of tubulin polymerization, binding of colchicine to tubulin, and cancer cell growth. ARDAP derivative 10 inhibited the proliferation of BCR/ABL-expressing KU812 and LAMA84 cells from chronic myeloid leukemia (CML) patients in blast crisis and of hematopoietic cells ectopically expressing the imatinib mesylate (IM) -sensitive KBM5-WT or its IM -resistant KBM5-T315I mutation. Compound 10 minimally affected the proliferation of normal blood cells, indicating that it may be a promising agent to overcome broad tyrosine kinase inhibitor resistance in relapsed/refractory CML patients. Compound 10 significantly decreased CML proliferation by inducing G2/M phase arrest and apoptosis via a mitochondria-dependent pathway. ARDAP 10 augmented the cytotoxic effects of IM in human CML cells. Compound 10 represents a robust lead compound to develop tubulin inhibitors with potential as novel treatments for CML.
• Identification of 3′,4′,5′-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells
  作者：Chih-Ho Lai、Yerra Koteswara Rao、Shih-Hua Fang、Yu-Ting Sing、Yew-Min Tzeng

  DOI：10.1016/j.bmcl.2010.07.094

  日期：2010.9

  Efforts to identify potent small molecule inhibitors of Helicobacter pylori led to the evaluation of 23 3',4',5'-trimethoxychalcone analogues. Some of the compounds displayed potent antibacterial activity against H. pylori. Three most active and selective compounds 1, 7, and 13 also showed the bactericide activity against the reference as well as multidrug-resistant strains of H. pylori. Additionally, the aforementioned three compounds potentially inhibited the H. pylori adhesion and invasion to human gastric epithelial (AGS) cells. Furthermore, these selective compounds inhibited the H. pylori-induced gastric inflammation by reduced inflammatory mediator's nuclear factor kappa B activation, and the secretion of interleukin-8. (c) 2010 Elsevier Ltd. All rights reserved.
• Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity
  作者：Sylvie Ducki、David Rennison、Meiko Woo、Alexander Kendall、Jérémie Fournier Dit Chabert、Alan T. McGown、Nicholas J. Lawrence

  DOI：10.1016/j.bmc.2009.09.039

  日期：2009.11

  The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC50 0.21 nM; combretastatin A4 CA4, IC50 2.0 nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC50 0.46 mu M; CA4, 0.10 mu M) and compete with [H-3] colchicine for binding to tubulin (8% [H-3] colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity. (C) 2009 Elsevier Ltd. All rights reserved.
• Anti-proliferative potential of triphenyl substituted pyrimidines against MDA-MB-231, HCT-116 and HT-29 cancer cell lines
  作者：Ashish Ranjan Dwivedi、Vijay Kumar、Harmeet Kaur、Naveen Kumar、Ravi Prakash Yadav、Ramarao Poduri、Somesh Baranwal、Vinod Kumar

  DOI：10.1016/j.bmcl.2020.127468

  日期：2020.10

  A series of triphenyl substituted pyrimidines as analogous of colchicine and combretastatin A-4 was synthesized and evaluated for the antiproliferative potential. The compounds were screened against MDA-MB-231, HCT-116 and HT-29 cell lines using MTT assay. Most of the compounds displayed antiproliferative activity in low to sub micro molar concentration. Amongst the synthesized derivatives, compounds HK-2, HK-10 and HK-13 were found to be effective against all the three cancer cell lines. HK-2 exhibited IC50 values of 3.39 mu M, 4.78 mu M and 4.23 mu M, HK-10 showed IC50 values of 0.81 mu M, 5.89 mu M, 4.96 mu M and HK-13 showed IC50 values 3.24 mu M, 4.93 mu M and 4.73 mu M against MDA-MB-231, HCT-116 and HT-29 cancer cell lines, respectively. HK-10 was found to be the most potent compound in the series with IC50 values of 0.81 mu M against MDA-MB-231. In the cell cycle analysis, HK-2 and HK-10 showed cell arrest at G2/M phase of the cell cycle while HK-13 inhibited cell growth at the G1/G0 phase. All the three compounds showed cell death induced through apoptosis. In the docking studies, HK-2, HK-10 and HK-13 were found to fit well in the colchicine binding site of the tubulin. Some of the compounds in the current series were found to be promising against all the three cancer cell lines and may act as potent leads for further development.