2-Hydroxy-3-methoxy-trans-zimtsaeure | 3626-94-6

• 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: 2-Hydroxy-3-methoxy-trans-zimtsaeure
• 英文别名: 2-hydroxy-3-methoxy-trans-cinnamic acid；2-hydroxy-3-methoxy-cinnamic acid；2-Hydroxy-3-methoxycinnamic acid；(E)-3-(2-hydroxy-3-methoxyphenyl)prop-2-enoic acid
• CAS: 3626-94-6
• 化学式: C₁₀H₁₀O₄
• 分子量: 194.187
• InChiKey: VZFPHVWLPRCAGD-AATRIKPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Hydroxy-3-methoxy-trans-zimtsaeure 在 sodium hydroxide 、 palladium on activated charcoal 作用下， 生成 8-甲氧基-3,4-二氢色烯-2-酮
  参考文献：
  名称：

  Borsche; Hahn-Weinheimer, Chemische Berichte, 1952, vol. 85, p. 198,201

  摘要：

  DOI：
• 作为产物：
  描述：

  8-甲氧基-2-氧代-2H-色烯-3-羧酸 在 甲醇 、 sodium methylate 、 铜 作用下， 生成 2-Hydroxy-3-methoxy-trans-zimtsaeure
  参考文献：
  名称：

  Borsche; Hahn-Weinheimer, Chemische Berichte, 1952, vol. 85, p. 198,201

  摘要：

  DOI：

文献信息

• Piperine–Chlorogenic Acid Hybrid Inhibits the Proliferation of the SK-MEL-147 Melanoma Cells by Modulating Mitotic Kinases
  作者：Carolina Pressete、Flávia Pereira Dias Viegas、Thâmara Gaspar Campos、Ester Siqueira Caixeta、João Adolfo Costa Hanemann、Guilherme Álvaro Ferreira-Silva、Bruno Zavan、Alexandre Ferro Aissa、Marta Miyazawa、Claudio Viegas、Marisa Ionta

  DOI：10.3390/ph16020145

  日期：——

  Melanoma is considered the most aggressive form of skin cancer, showing high metastatic potential and persistent high mortality rates despite the introduction of immunotherapy and targeted therapies. Thus, it is important to identify new drug candidates for melanoma. The design of hybrid molecules, with different pharmacophore fragments combined in the same scaffold, is an interesting strategy for obtaining new multi-target and more effective anticancer drugs. We designed nine hybrid compounds bearing piperine and chlorogenic acid pharmacophoric groups and evaluated their antitumoral potential on melanoma cells with distinct mutational profiles SK-MEL-147, CHL-1 and WM1366. We identified the compound named PQM-277 (3a) to be the most cytotoxic one, inhibiting mitosis progression and promoting an accumulation of cells in pro-metaphase and metaphase by altering the expression of genes that govern G2/M transition and mitosis onset. Compound 3a downregulated FOXM1, CCNB1, CDK1, AURKA, AURKB, and PLK1, and upregulated CDKN1A. Molecular docking showed that 3a could interact with the CUL1-RBX1 complex, which activity is necessary to trigger molecular events essential for FOXM1 transactivation and, in turn, G2/M gene expression. In addition, compound 3a effectively induced apoptosis by increasing BAX/BCL2 ratio. Our findings demonstrate that 3a is an important antitumor candidate prototype and support further investigations to evaluate its potential for melanoma treatment, especially for refractory cases to BRAF/MEK inhibitors.

  黑色素瘤被认为是皮肤癌中最具侵略性的形式，表现出高转移潜力和持续的高死亡率，尽管引入了免疫疗法和靶向治疗，但仍然很重要识别黑色素瘤的新药物候选者。设计混合分子，将不同的药效团片段组合在同一支架中，是获得新的多靶点和更有效的抗癌药物的有趣策略。我们设计了九种带有胡椒碱和绿原酸药效团的混合化合物，并评估它们对黑色素瘤细胞的抗肿瘤潜力，这些细胞具有不同的突变谱系SK-MEL-147、CHL-1和WM1366。我们确定了名为PQM-277（3a）的化合物是最具细胞毒性的化合物，通过改变调控G2/M转换和有丝分裂起始的基因的表达，抑制有丝分裂进程，并促进细胞在前中期和中期的积累。化合物3a下调了FOXM1、CCNB1、CDK1、AURKA、AURKB和PLK1，上调了CDKN1A。分子对接显示，3a可以与CUL1-RBX1复合物相互作用，这种活性对于触发FOXM1转录激活以及G2/M基因表达至关重要。此外，化合物3a通过增加BAX/BCL2比例有效诱导细胞凋亡。我们的研究结果表明，3a是一个重要的抗肿瘤候选原型，并支持进一步研究以评估其在黑色素瘤治疗中的潜力，尤其是对于BRAF/MEK抑制剂难治性病例。
• Enzymatic synthesis of kavalactones and flavokavains
  申请人：Whitehead Institute for Biomedical Research

  公开号：US10941429B2

  公开（公告）日：2021-03-09

  Disclosed are methods, compositions, proteins, nucleic acids, cells, vectors, compounds, reagents, and systems for the preparation of kavalactones, flavokavains, and kavalactone and flavokavain biosynthetic intermediates using enzymes expressed in heterologous host cells, such as microorganisms or plants, or using in vitro enzymatic reactions. This invention also provides for the expression of the enzymes by recombinant cell lines and vectors. Furthermore, the enzymes can be components of constructs such as fusion proteins. The kavalactones produced can be utilized to treat anxiety disorder, insomnia, and other psychological and neurological disorders. The flavokavains produced can be utilized to treat various cancers including colon, bladder, and breast cancers.

  本发明公开了利用在异源宿主细胞（如微生物或植物）中表达的酶或利用体外酶促反应制备卡瓦内酯、黄酮素以及卡瓦内酯和黄酮素生物合成中间体的方法、组合物、蛋白质、核酸、细胞、载体、化合物、试剂和系统。本发明还提供了通过重组细胞系和载体表达酶的方法。此外，酶还可以是融合蛋白等构建体的组成部分。生产的卡瓦内酯可用于治疗焦虑症、失眠症以及其他心理和神经疾病。生产的黄酮类化合物可用于治疗各种癌症，包括结肠癌、膀胱癌和乳腺癌。
• Methods and reagents for the treatment of metabolic disorders
  申请人：Lee S. Margaret

  公开号：US20060069161A1

  公开（公告）日：2006-03-30

  The invention features compositions, methods, and kits for the treatment of metabolic disorders such as diabetes and obesity.

  本发明的特点是用于治疗糖尿病和肥胖症等代谢性疾病的组合物、方法和试剂盒。
• Dey; Kutti, Proceedings of the National Institute of Sciences of India, 1940, vol. 6, p. 641,656
  作者：Dey、Kutti

  DOI：——

  日期：——
• A one-pot synthesis of 3-amino-3-arylpropionic acids
  作者：C.Y.K. Tan、D.F. Weaver

  DOI：10.1016/s0040-4020(02)00824-4

  日期：2002.9

  3-Aminopropionic acids (beta-amino acids) are biologically active compounds of interest in medicinal and pharmaceutical chemistry. Twenty-one 3-amino-3-arylpropionic acids were synthesized via a facile one-pot synthesis. In addition, a series of mechanistic studies have been performed to optimize the production of these beta-amino acids. The reaction mechanism of this one-pot synthesis of beta-amino acids, as well as the electronic effect of para-substitution and the influence of solvent polarity on the proposed reaction mechanism are discussed. (C) 2002 Elsevier Science Ltd. All rights reserved.

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