(E)-3-(3,4,5-trimethoxyphenyl)-2-(3,4-dimethoxyphenyl)acrylic acid | 1228170-25-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: (E)-3-(3,4,5-trimethoxyphenyl)-2-(3,4-dimethoxyphenyl)acrylic acid
• 英文别名: (E)-2-(3,4-dimethoxyphenyl)-3-(3,4,5-trimethoxyphenyl)acrylic acid
• CAS: 1228170-25-9
• 化学式: C₂₀H₂₂O₇
• 分子量: 374.39
• InChiKey: JFQGGVFZDUIVFJ-RIYZIHGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.35
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  83.45
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  (E)-3-(3,4,5-trimethoxyphenyl)-2-(3,4-dimethoxyphenyl)acrylic acid 在 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 7.0h， 生成 (E)-2-(3,4-dimethoxyphenyl)-N'-((Z)-2-oxoindolin-3-ylidene)-3-(3,4,5-trimethoxyphenyl)acrylohydrazide
  参考文献：
  名称：

  开发作为抗有丝分裂剂的酰肼腙-栓系的考布他汀-羟吲哚衍生物

  摘要：

  以( E )-双(苯基)丙烯酰肼和取代靛红为合成前体，通过缩合反应合成了一系列新的考布他汀-羟吲哚衍生物，通过酰肼腙连接。为了确定这些新衍生物的潜力，使用不同的癌细胞系评估了体外细胞毒活性，特别是肺癌、结直肠癌、乳腺癌和皮肤来源的癌细胞系。还对 HaCaT 细胞上最有效的化合物9o进行了可行性研究，表明其对非恶性细胞系无毒。细胞活力测定表明，在 A 环和N环上具有三甲氧基取代的衍生物9o靛红环上的 - 苄基取代对肺癌 (A549) 细胞系表现出有效的抗癌活性，IC 50值为 1.26±1.03 µM。此外，使用 DAPI、AO/EB 进行染色研究以确定核形态变化、DNA 损伤和细胞凋亡的诱导，膜联蛋白 V-FITC/PI 测定也证实了这一点，表明细胞生长抑制涉及细胞凋亡机制。此外，化合物9o对 ROS 产生的诱导作用表明 ROS 介导的不需要细胞的细胞死亡以及细胞凋亡的调节。从 G2/M 期细胞周期停滞和化合物9o

  DOI：

  10.1016/j.molstruc.2022.134675
• 作为产物：
  描述：

  3,4-二甲氧基苯乙酸 、 3,4,5-三甲氧基苯甲醛 在 乙酸酐 、 三乙胺 作用下， 生成 (E)-3-(3,4,5-trimethoxyphenyl)-2-(3,4-dimethoxyphenyl)acrylic acid
  参考文献：
  名称：

  过渡金属催化氧化锍和碘鎓叶立德与顺式芪酸环化合成α-吡喃酮和chromen-2-ones

  摘要：

  已经开发了一种过渡金属催化的卡宾插入策略来激活药用重要的顺式-芪酸的失活 sp 2 C-H 键。这种方法能够在顺式的烯烃键上轻松构建 α-pyrone 和 chromene-2-one 骨架-芪酸具有高原子经济性、良好的收率、广泛的官能团耐受性和克级合成可行性。该策略揭示了酸官能团作为导向基团以及作为卡宾前体的锍和高价碘叶立德的效率。探索了构建的结构的光物理特性，显示发射范围为 500 至 600 nm，并通过分子对接分析和百分比抑制研究检查了生物潜力。此外，还进行了 ESI-MS 研究以确定关键中间体，帮助勾勒出可能的机制。

  DOI：

  10.1039/d2nj03454a

文献信息

• Synthesis, Antibacterial and Pharmacokinetic Evaluation of Novel Derivatives of Harmine N9-Cinnamic Acid
  作者：Yan Liang、Dian He、Deshun Zhou、Junshuai Li、Lei Tang、Zhen Wang

  DOI：10.3390/molecules26164842

  日期：——

  A series of 16 new derivatives of harmine N9-Cinnamic acid were synthesized and fully characterized using NMR and MS. The in vitro antibacterial evaluation revealed that most of the synthesized harmine derivatives displayed better antibacterial activities against Gram-positive strains (S. aureus, S. albus and MRSA) than Gram-negative strains (E. coli and PA). In particular, compound 3c showed the strongest bactericidal activity with a minimum inhibitory concentration of 13.67 μg/mL. MTT assay showed that compound 3c displayed weaker cytotoxicity than harmine with IC50 of 340.30, 94.86 and 161.67 μmol/L against WI-38, MCF-7 and HepG2 cell lines, respectively. The pharmacokinetic study revealed that the distribution and elimination of 3c in vivo were rapid in rats with an oral bioavailability of 6.9%.

  一系列16个新的harmine N9-肉桂酸衍生物被合成并通过NMR和MS进行了全面表征。体外抗菌评价显示，大多数合成的harmine衍生物对革兰氏阳性菌株（金黄色葡萄球菌、白色葡萄球菌和MRSA）的抗菌活性优于革兰氏阴性菌株（大肠杆菌和假单胞菌）。特别是，化合物3c显示出最强的杀菌活性，最小抑制浓度为13.67 μg/mL。MTT试验显示，化合物3c对WI-38、MCF-7和HepG2细胞系的细胞毒性较harmine更弱，IC50分别为340.30、94.86和161.67 μmol/L。药代动力学研究表明，3c在体内的分布和消除在大鼠中迅速，口服生物利用度为6.9%。
• Synthesis, mitochondrial localization of fluorescent derivatives of cinnamamide as anticancer agents
  作者：Kun Yang、Yuanyuan Li、Qun Tang、Lifang Zheng、Dian He

  DOI：10.1016/j.ejmech.2019.03.001

  日期：2019.5

  Mitochondria are considered as a therapeutic target for new drug design toward all kinds of cancer. Hence in order to enhance the dosage in mitochondrial fraction of cinnamamides, the mitochondria targeted derivatives were designed by the incorporation of cinnamamides into a fluorophore carrier of coumarin-3-carboxamide with a 1:1 stoichiometry. Using the amide linkers, twenty-one compounds were synthesized and the cytotoxicity against a panel of cancer cells (MCF-7, Hela, HepG2, HL-60) was tested. In particular, compound 18c displayed the potent cytotoxicity toward HL-60 leukaemia cells, which could quickly and efficiently entry into HL-60 cells and specifically localize within mitochondria. And 18c preferred enrichment in HL-60 cells than in PBMC normal cells, accounting for the higher toxicity to cancer cells than to normal cells. Moreover, the dissipations of mitochondrial membrane potential and enhancement of cellular ROS level were also preceded upon 18c treatment, leading to cell cycle arrest and apoptosis/necrosis in HL-60 cells. Besides, acted as a Michael acceptor, 18c initiated a thia-Michael addition reaction toward cysteamine (1:2 stoichiometry), detecting by the UV-Vis spectrum and HRMS analysis. This could result in the blue emission of 18c in mitochondria after the procedure of cell fixation, owing to the formation of covalent bond with mitochondrial thiols. Our study reported 18c might be useful for the further development into a mitochondria-targeted anti-leukemia agent and the Michael acceptor might be a versatile functional group. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Pyrazolone-fused combretastatins and their precursors: synthesis, cytotoxicity, antitubulin activity and molecular modeling studies
  作者：Bojan Burja、Tamara Čimbora-Zovko、Sanja Tomić、Tihana Jelušić、Marijan Kočevar、Slovenko Polanc、Maja Osmak

  DOI：10.1016/j.bmc.2010.03.006

  日期：2010.4

  A series of pyrazolone-fused combretastatins and precursors were synthesized and their cytotoxicity as well as antitubulin potential was evaluated. The hydrazide 9f and the pyrazolone-fused combretastatins 12a, 12b and 12c were highly cytotoxic against various tumor cell lines including cisplatin resistant cells. The same compounds were also the best inhibitors of tubulin polymerization. Molecular modeling results showed that they bind the colchicine binding site at the tubulin heterodimer. The hydrazide 9f arrested HeLa cells in the G2/M phase of the cell cycle and strongly affected cell shape and microtubule network. (C) 2010 Elsevier Ltd. All rights reserved.