(E)-3-(4-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one | 861881-92-7

• 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: (E)-3-(4-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• 英文别名: (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(4-chlorophenyl)-2-propen-1-one；(2E)-3-(4-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 861881-92-7
• 化学式: C₁₈H₁₇ClO₄
• 分子量: 332.784
• InChiKey: QVVHIXSRYJFOLF-RMKNXTFCSA-N

物化性质

• 熔点：
  115-116 °C
• 沸点：
  495.3±45.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (E)-3-(4-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one 在 对甲基苯磺酰甲基异腈 、 sodium hydride 作用下， 以 乙醚 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 4.0h， 以82%的产率得到(4-(4-chlorophenyl)-1H-pyrrol-3-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  Structure-activity relationship studies and in vitro and in vivo anticancer activity of novel 3-aroyl-1,4-diarylpyrroles against solid tumors and hematological malignancies

  摘要：

  Novel 3-aroyl-1,4-diarylpyrrole derivatives were synthesized to explore structure-activity relationships at the phenyls at positions 1 and 4 of the pyrrole. The presence of amino phenyl rings at positions 1 and 4 of the pyrrole ring were found to be a crucial requirement for potent antitumor activity. Several compounds strongly inhibited tubulin assembly through binding to the colchicine site. Compounds 42, 44, 48, 62 and 69 showed antitumor activity with low nanomolar 1050 values in several cancer cell lines. Compound 48 was generally more effective as an inhibitor of glioblastoma, colorectal and urinary bladder cancer cell lines; 69 consistently inhibited CML cell lines and demonstrated superiority in nilotinib and imatinib resistant LAMA84-R and KBM5-T3151 cells. In animal models, compound 48 exhibited significant inhibition of the growth of T24 bladder carcinoma and ES-2 ovarian clear cell carcinoma tumors. Compounds 48 and 69 represent robust lead compounds for the design of new broadspectrum anticancer agents active in different types of solid and hematological tumors. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.111828
• 作为产物：
  描述：

  3',4',5'-三甲氧基苯乙酮 、 4-氯苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 (E)-3-(4-chlorophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  作为具有抗肿瘤效力的微管蛋白聚合抑制剂的一系列新型苯并噻嗪衍生物

  摘要：

  在这项工作中，合成并筛选了一系列二芳基苯并[ b ] [1,4] 硫氮杂衍生物D1-D36作为具有抗肿瘤效力的微管蛋白聚合抑制剂。它们是通过首次引入七元环苯并噻嗪作为 CA-4 修饰的接头而设计的。其中，命中化合物D8显示出抑制多种癌细胞系生长的潜力（IC 50值：HeLa 1.48 μM，MCF-7 1.47 μM，HT29 1.52 μM 和 A549 1.94 μM），与阳性对照秋水仙碱和CA-4P。D8的计算 IC 50值作为微管蛋白聚合抑制剂的浓度为 1.20 μM。流式细胞术检测结果表明，D8可以诱导有丝分裂灾难和活癌细胞的死亡。D8还表明了抗血管活性。对接模拟暗示了可能的结合模式，推断引入与附近微管蛋白链相互作用的可能性。由于新的结构试验已经进行了初步讨论，这项工作可能会激发进一步修改微管蛋白相关抗癌药物和治疗方法的新思路。

  DOI：

  10.1016/j.bioorg.2020.104585

文献信息

• Design, synthesis and cytotoxic activity of certain novel chalcone analogous compounds
  作者：S. El-Meligie、Azza T. Taher、Aliaa M. Kamal、A. Youssef

  DOI：10.1016/j.ejmech.2016.09.099

  日期：2017.1

  of chalcone analogous compounds were designed and synthesized. Replacing/substituting the enone or ethylenic bridge of the parent chalcone with rigid heterocyclic moieties or substituted aromatic amines gave nineteen target compounds. Their cytotoxic activities were screened against both breast and liver cancer cells as well as breast and liver normal cells. Target compounds were also evaluated for

  设计并合成了一系列查尔酮类似化合物。用刚性杂环部分或取代的芳族胺取代/取代母体查尔酮的烯酮或烯键，得到十九种目标化合物。筛选了针对乳腺癌和肝癌细胞以及乳腺癌和肝正常细胞的细胞毒性活性。还评估了目标化合物对微管蛋白β聚合的抑制活性。目标化合物2e，3a，3b，3c，4a-4d，5a，5b和6显示出对MCF-7和HepG2均具有广谱优异的抗癌活性。化合物4a显示出最大的TUBb抑制活性。
• Study on the substituents' effects of a series of synthetic chalcones against the yeast Candida albicans
  作者：D. Batovska、St. Parushev、A. Slavova、V. Bankova、I. Tsvetkova、M. Ninova、H. Najdenski

  DOI：10.1016/j.ejmech.2006.08.012

  日期：2007.1

  A large series of chalcones were synthesized and studied for activity against Candida albicans. The SAR analysis showed that the antifungal activity was highly dependent on the substitution pattern of the aryl rings and correlated to a large extent with the ability of compounds to interact with sulfhydryl groups. The most active were the hydroxylated chalcones as their activity related to the location

  合成了大量查耳酮，并研究了其对白色念珠菌的活性。SAR分析表明，抗真菌活性高度依赖于芳基环的取代方式，并在很大程度上与化合物与巯基相互作用的能力有关。最具活性的是羟基化查耳酮，因为它们的活性与芳基环B中酚基的位置有关，如下所示：o-OH> p-OH约为3,4-di-OH> m-OH。获得的这些相关性和其他相关性极大地有助于设计抗候选查耳酮。
• Trimethoxy Crown Chalcones as Multifunctional Class of Monoamine Oxidase Enzyme Inhibitors
  作者：Naseer Maliyakkal、Gulberk Ucar、Bijo Mathew、Ipek Baysal、Anandkumar Tengli、Mohammad Ali Abdullah Almoyad、Della Grace Thomas Parambi、Nicola Gambacorta、Orazio Nicolotti、Asmy Appadath Beeran

  DOI：10.2174/1386207324666210603125452

  日期：2022.7

  Chalcones with methoxy substituent are considered as a promising framework for the inhibition of monoamine oxidase (MAO) enzymes.

  A series of nine trimethoxy substituted chalcones (TMa-TMi) was synthesized and evaluated as a multifunctional class of MAO inhibitors. All the synthesized compounds were investigated for their in vitro MAO inhibition, kinetics, reversibility, blood-brain barrier (BBB) permeation, and cytotoxicity and antioxidant potentials.

  In the present study, compound (2E)-3-(4-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)prop- 2-en-1-one (TMf) was provided with a MAO-A inhibition constant value equal to 3.47±0.09 μM with a selectivity of 0.008, thus comparable to that of moclobemide, a well known potent hMAOA inhibitor (SI=0.010). Compound (2E)-3-(4-bromophenyl)-1-(3,4,5-trimethoxyphenyl)prop-2- en-1-one (TMh) show good MAO-B inhibition with inhibition constant of 0.46±0.009 μM. The PAMPA assay demonstrated that all the synthesized derivatives can cross the BBB successfully. The cytotoxicity studies revealed that TMf and TMh have 88.22 and 80.18 % cell viability at 25 μM. Compound TMf appeared as the most promising antioxidant molecule with IC50 values, relative to DPPH and H2O2 radical activities equal to 6.02±0.17 and 7.25±0.07 μM. To shed light on the molecular interactions of TMf and TMh towards MAO-A and MAO-B, molecular docking simulations and MM/GBSA calculations have been carried out.

  The lead molecules TMf and TMh with multi-functional nature can be further employed for the treatment of various neurodegenerative disorders and depressive states.

  背景： 具有甲氧基取代基的查耳酮被认为是一种有前途的 抑制单胺氧化酶 (MAO) 的框架。 研究方法： 合成了九种三甲氧基取代的查耳酮（TMa-TMi）系列，并将其作为一种多功能 MAO 作为一种多功能 MAO 抑制剂进行了评估。对所有合成的化合物进行了 的体外 MAO 抑制、动力学、可逆性、血脑屏障（BBB）渗透性和细胞毒性进行了研究。 渗透性、细胞毒性和抗氧化潜力进行了研究。 研究结果 在本研究中，化合物 (2E)-3-(4-nitrophenyl)-1-(3,4,5-trimethoxyphenyl)prop- 2-烯-1-酮（TMf）的 MAO-A 抑制常数为 3.47±0.09 μM 选择性为 0.008，因此与众所周知的强效 hMAOA 抑制剂吗氯贝胺相当（SI=0.008）。 的选择性相当（SI=0.010）。化合物(2E)-3-(4-溴苯基)-1-(3,4,5-三甲氧基苯基)丙-2-烯-1-酮（TMh 烯-1-酮（TMh）对 MAO-B 有良好的抑制作用，抑制常数为 0.46±0.009 μM。PAMPA PAMPA 试验表明，所有合成的衍生物都能成功穿过 BBB。 细胞毒性研究表明，TMf 和 TMh 的细胞存活率分别为 88.22% 和 80.18%，在 25 微米。化合物 TMf 是最有前途的抗氧化分子，其 IC50 值为 分别为 6.02±0.17 和 7.25±0.07 μM。为了揭示 为揭示 TMf 和 TMh 对 MAO-A 和 MAO-B 的分子相互作用，进行了分子对接模拟和 MM/GBSA 计算。 模拟和 MM/GBSA 计算。 研究结论 具有多功能性质的先导分子 TMf 和 TMh 可以进一步 用于治疗各种神经退行性疾病和抑郁状态。
• 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.
• Synthesis and biological evaluation of chalcones and their derived pyrazoles as potential cytotoxic agents
  作者：B.A. Bhat、K.L. Dhar、S.C. Puri、A.K. Saxena、M. Shanmugavel、G.N. Qazi

  DOI：10.1016/j.bmcl.2005.03.121

  日期：2005.6

  A series of substituted chalcones and their corresponding pyrazoles were synthesized and evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Out of 93 compounds screened, 8 compounds, 1s, 3i,j,n, 4i,j,n and 4s, showed marked activity. Compounds 4j,n and 4s were found to be the most promising in this study. SAR is also discussed. (c) 2005 Elsevier Ltd. All rights reserved.