7-(3-bromopropoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one | 862255-02-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 7-(3-bromopropoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one
• 英文别名: 7-(3-Bromopropoxy)-5-hydroxy-3-(4-hydroxyphenyl)chromen-4-one
• CAS: 862255-02-5
• 化学式: C₁₈H₁₅BrO₅
• 分子量: 391.218
• InChiKey: AJGLTUKQQZKQIE-UHFFFAOYSA-N

物化性质

• 熔点：
  124-126 °C(Solv: acetone (67-64-1))
• 沸点：
  617.7±55.0 °C(Predicted)
• 密度：
  1.588±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7-(3-bromopropoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one 在 氯化亚砜 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 96.0h， 生成 7-[3-[bis(2-chloroethyl)amino]propoxy]-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one
  参考文献：
  名称：

  类黄酮氮芥子衍生物的合成及其体外抗肿瘤活性的研究。

  摘要：

  合成了几种新颖的类黄酮氮芥子衍生物，并通过体外MTT分析评估了其对七种人类癌细胞系（HeLa，A549，HepG2，MCF7，SH-SY5Y，PC-3，DU145）的抗增殖活性。所得的IC 50显示大多数化合物对七种细胞系表现出更好的抑制活性。一些化合物的IC50值低于众所周知的美法仑。特别是，化合物8b是抑制HeLa细胞的最有前途的化合物，IC50值为1.43μM。它对这七个细胞系显示出极好的抗肿瘤活性。此外，它可以阻止HeLa在G2 / M期的细胞周期并诱导细胞凋亡。线粒体膜电位的丧失可能是细胞凋亡的介导因子。

  DOI：

  10.1016/j.bioorg.2020.103613
• 作为产物：
  描述：

  染料木素 、 1,3-二溴丙烷 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 8.25h， 以69%的产率得到7-(3-bromopropoxy)-5-hydroxy-3-(4-hydroxyphenyl)-4H-chromen-4-one
  参考文献：
  名称：

  类黄酮氮芥子衍生物的合成及其体外抗肿瘤活性的研究。

  摘要：

  合成了几种新颖的类黄酮氮芥子衍生物，并通过体外MTT分析评估了其对七种人类癌细胞系（HeLa，A549，HepG2，MCF7，SH-SY5Y，PC-3，DU145）的抗增殖活性。所得的IC 50显示大多数化合物对七种细胞系表现出更好的抑制活性。一些化合物的IC50值低于众所周知的美法仑。特别是，化合物8b是抑制HeLa细胞的最有前途的化合物，IC50值为1.43μM。它对这七个细胞系显示出极好的抗肿瘤活性。此外，它可以阻止HeLa在G2 / M期的细胞周期并诱导细胞凋亡。线粒体膜电位的丧失可能是细胞凋亡的介导因子。

  DOI：

  10.1016/j.bioorg.2020.103613

文献信息

• 染料木素衍生物、其制备方法及应用
  申请人：北京师范大学

  公开号：CN108164490B

  公开（公告）日：2020-08-14

  本发明提供了一种染料木素衍生物，如式(I)所示，其中，R为C1～C5的烷基或C6～C10的芳基；n为大于等于1的整数。与现有技术相比，本发明提供的染料木素衍生物对多种肿瘤细胞具有良好的生长抑制作用，尤其是当n为2～4的整数时，对于A549细胞、Hela细胞与HepG2三类肿瘤细胞具有较高的抑制生长活性，并能够与CDK2酶及FAK酶发生作用，干扰其活性。
• 染料木素桥连咪唑类衍生物合成方法及其抗肿瘤方向应用
  申请人：北京师范大学

  公开号：CN109180655A

  公开（公告）日：2019-01-11

  本发明提供了一种染料木素衍生物，如式(I)所示，其中，R为含氮杂环基或取代的含氮杂环基；所述取代的含氮杂环基中取代基选自C1～C10的烷基；n为大于等于1的整数。与现有技术相比，本发明提供的染料木素衍生物对多种肿瘤细胞具有良好的生长抑制作用，尤其是当n为3时，对于A549细胞、Hela细胞与HepG2三类肿瘤细胞具有较高的抑制生长活性。
• Synthesis and Chemopreventive Potential of 5-FU/Genistein Hybrids on Colorectal Cancer Cells
  作者：Gustavo Moreno-Quintero、Wilson Castrillón-Lopez、Angie Herrera-Ramirez、Andrés F. Yepes-Pérez、Jorge Quintero-Saumeth、Wilson Cardona-Galeano

  DOI：10.3390/ph15101299

  日期：——

  A series of 5-FU-Genistein hybrids were synthesized and their structures were elucidated by spectroscopic analysis. The chemopreventive potential of these compounds was evaluated in human colon adenocarcinoma cells (SW480 and SW620) and non-malignant cell lines (HaCaT and CHO-K1). Hybrid 4a displayed cytotoxicity against SW480 and SW620 cells with IC50 values of 62.73 ± 7.26 µM and 50.58 ± 1.33 µM, respectively; compound 4g induced cytotoxicity in SW620 cells with an IC50 value of 36.84 ± 0.71 µM. These compounds were even more selective than genistein alone, the reference drug (5-FU) and the equimolar mixture of genistein plus 5-FU. In addition, hybrids 4a and 4g induced time- and concentration-dependent antiproliferative activity and cell cycle arrest at the S-phase and G2/M. It was also observed that hybrid 4a induced apoptosis in SW620 cells probably triggered by the extrinsic pathway in response to the activation of p53, as evidenced by the increase in the levels of caspases 3/8 and the tumor suppressor protein (Tp53). Molecular docking studies suggest that the most active compound 4a would bind efficiently to proapoptotic human caspases 3/8 and human Tp53, which in turn could provide valuable information on the biochemical mechanism for the in vitro cytotoxic response of this compound in SW620 colon carcinoma cell lines. On the other hand, molecular dynamics (MD) studies provided strong evidence of the conformational stability of the complex between caspase-3 and hybrid 4a obtained throughout 100 ns all-atom MD simulation. Molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analyses of the complex with caspase-3 showed that the interaction between the ligand and the target protein is stable. Altogether, the results suggest that the active hybrids, mainly compound 4a, might act by modulating caspase-3 activity in a colorectal cancer model, making it a privileged scaffold that could be used in future investigations.

  我们合成了一系列 5-FU -染料木素混合物，并通过光谱分析阐明了它们的结构。在人结肠腺癌细胞（SW480 和 SW620）和非恶性细胞系（HaCaT 和 CHO-K1）中评估了这些化合物的化学预防潜力。杂交化合物 4a 对 SW480 和 SW620 细胞具有细胞毒性，IC50 值分别为 62.73 ± 7.26 µM 和 50.58 ± 1.33 µM；化合物 4g 对 SW620 细胞具有细胞毒性，IC50 值为 36.84 ± 0.71 µM。这些化合物的选择性甚至高于单独的染料木素、参考药物（5-FU）以及染料木素和 5-FU 的等摩尔混合物。此外，杂交化合物 4a 和 4g 诱导了时间和浓度依赖性的抗增殖活性，并使细胞周期停滞在 S 期和 G2/M。研究还观察到，杂交种 4a 可诱导 SW620 细胞凋亡，这可能是由 p53 激活后的外显子通路触发的，caspases 3/8 和肿瘤抑制蛋白（Tp53）水平的升高证明了这一点。分子对接研究表明，活性最强的化合物 4a 能与促凋亡的人类 caspases 3/8 和人类 Tp53 有效结合，这反过来又能为该化合物在 SW620 结肠癌细胞系中产生体外细胞毒性反应的生化机制提供有价值的信息。另一方面，分子动力学（MD）研究提供了强有力的证据，证明在 100 ns 全原子 MD 模拟中获得的 caspase-3 与杂交 4a 复合物的构象稳定性。分子力学泊松-玻尔兹曼表面积（MM-PBSA）分析表明，配体与目标蛋白之间的相互作用是稳定的。总之，研究结果表明，在结直肠癌模型中，活性杂交化合物（主要是化合物 4a）可能会通过调节 caspase-3 的活性而发挥作用，使其成为一种可用于未来研究的特殊支架。
• Design, synthesis and evaluation of genistein-O-alkylbenzylamines as potential multifunctional agents for the treatment of Alzheimer's disease
  作者：Xiaoming Qiang、Zhipei Sang、Wen Yuan、Yan Li、Qiang Liu、Ping Bai、Yikun Shi、Wei Ang、Zhenghuai Tan、Yong Deng

  DOI：10.1016/j.ejmech.2014.02.045

  日期：2014.4

  A series of genistein derivatives with carbon spacer-linked alkylbenzylamines were designed, synthesized and tested as multifunctional agents for the treatment of Alzheimer's disease (AD). The results showed that most of these compounds exhibited good acetylcholinesterase (AChE) inhibitory activity, with moderate-to-good anti-oxidative activity. Specifically, compounds 10b, 19d and 254 exhibited significant inhibition of beta-amyloid (A beta) aggregation and exhibited metal chelating properties. In particular, 25d inhibited: self-induced A beta(1-42) aggregation, Cu2+-induced A beta(1-42) aggregation, and human AChE-induced A beta(1-40) aggregation by 35%, 77.8%, and 36.2%, respectively. Moreover, both kinetic analysis of AChE inhibition and the molecular modeling study suggested that 25d binds simultaneously to catalytic active site and peripheral anionic site of AChE. More importantly, compound 25d disassembled the well-structured A beta fibrils generated by Cu2+-induced A beta aggregation by 72.1%. Furthermore, the step-down passive avoidance test showed this compound significantly reversed scopolamine-induced memory deficit in mice. These results suggest that 25d may be a promising multifunctional agent for AD treatment. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and biological evaluation of genistein-<i>O</i> -alkylamine derivatives as potential multifunctional anti-Alzheimer agents
  作者：Chen Hong、Hui-yan Guo、Shuai Chen、Jian-wu Lv、Xin Zhang、Ya-cheng Yang、Kang Huang、Yi-juan Zhang、Zhi-yong Tian、Wen Luo、Yi-ping Chen

  DOI：10.1111/cbdd.13414

  日期：2019.2

  AbstractA series of genistein derivatives were synthesized and evaluated as multifunctional anti‐Alzheimer agents. The results showed that these derivatives had significant acetylcholinesterase (AChE) inhibitory activity; compound 5a exhibited the strongest inhibition to AChE with an IC50 value (0.034 μM) much lower than that of rivastigmine (6.53 μM). A Lineweaver–Burk plot and molecular modeling study showed that compound 5a targeted both the catalytic active site and the peripheral anionic site of AChE. These compounds also showed potent peroxy scavenging activity and metal‐chelating ability. The compounds did not show obvious effect on HepG2 and PC12 cell viability at the concentration of 100 μM. Therefore, these genistein derivatives can be utilized as multifunctional agents for the treatment of AD.