2,2'-[(5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromen-3,7-di-yl)bis(oxy)]diacetic acid ethyl ester

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2,2'-[(5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromen-3,7-di-yl)bis(oxy)]diacetic acid ethyl ester
• 英文别名: diethyl 2,2'-{[5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromene-3,7-diyl]bis(oxy)}diacetate；Ethyl 2-[3-(2-ethoxy-2-oxoethoxy)-5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-4-oxochromen-7-yl]oxyacetate；ethyl 2-[3-(2-ethoxy-2-oxoethoxy)-5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-enyl)-4-oxochromen-7-yl]oxyacetate
• 化学式: C₂₉H₃₂O₁₀
• 分子量: 540.567
• InChiKey: XDMQAZDIBZRQSZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  39
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2,2'-[(5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromen-3,7-di-yl)bis(oxy)]diacetic acid ethyl ester 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 2,2'-[(5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromen-3,7-diyl)bis(oxy)]diacetic acid
  参考文献：
  名称：

  半合成的黄酮类抗生素具有抗甲氧西林金黄色葡萄球菌（MRSA）的治疗潜力

  摘要：

  从天然icaritin设计了一系列新的基于半黄酮的模拟抗菌肽的小分子，以对抗耐药的革兰氏阳性细菌感染。含有两个精氨酸残基的化合物6对革兰氏阳性细菌（包括MRSA）表现出优异的抗菌活性，并且对哺乳动物细胞的毒性极低，因此与临床试验中的几种具有膜活性的抗生素相比，其选择性高达511以上。我们的数据首次表明，icaritin衍生物可有效杀死细菌。同时，这是第一项采用仿生策略来设计有效的基于黄酮的膜靶向抗菌剂的研究。6通过破坏细菌膜表现出快速的杀菌活性，可以规避细菌抗药性的发展。重要的是，6在由MRSA和金黄色葡萄球菌引起的角膜感染的小鼠模型中非常有效。

  DOI：

  10.1021/acs.jmedchem.7b00380
• 作为产物：
  描述：

  去水淫羊藿黄素 、 溴乙酸乙酯 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 6.0h， 以90%的产率得到2,2'-[(5-hydroxy-2-(4-methoxyphenyl)-8-(3-methylbut-2-en-1-yl)-4-oxo-4H-chromen-3,7-di-yl)bis(oxy)]diacetic acid ethyl ester
  参考文献：
  名称：

  Synthesis and cancer cell growth inhibitory activity of icaritin derivatives

  摘要：

  A series of icaritin derivatives bearing carboxylic acid or carboxylic ester groups are synthesized, and their in vitro cytotoxic activity against three cancer cell lines, MCF-7, MDA-MB-435s, and A549, are evaluated by MTT assay. Several derivatives including 2h, 2j, 5b and 5d show higher cytotoxic activity than the parent compound icaritin against these cancer cell lines. Compounds 5b and 5d are even more cytotoxic to MCF-7 cells than the clinic drug tamoxifen. Moreover, compound 5b is found to be non-toxic to normal cells (Vero) and both 5b and 5d exhibit good selectivity towards estrogen receptor positive MCF-7 breast cancer cells over estrogen receptor negative MDA-MB-435s breast cancer cells. The structure activity relationship analysis has revealed that mono-substitution at either C-3 or C-7 hydroxyl group of icaritin could improve the cytotoxicity of icaritin, and the C-3 hydroxyl group may be a preferable site for chemical modification. In addition, the length, the flexibility and the additional branching substituent group of the substitution chain(s) at both C-3 and C-7 hydroxyl groups can all affect the anticancer activity of these derivatives. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.06.006

文献信息

• Synthesis and cancer cell growth inhibitory activity of icaritin derivatives
  作者：Chen Wang、Ping Wu、Jing-Fang Shi、Zi-Hua Jiang、Xiao-Yi Wei

  DOI：10.1016/j.ejmech.2015.06.006

  日期：2015.7

  A series of icaritin derivatives bearing carboxylic acid or carboxylic ester groups are synthesized, and their in vitro cytotoxic activity against three cancer cell lines, MCF-7, MDA-MB-435s, and A549, are evaluated by MTT assay. Several derivatives including 2h, 2j, 5b and 5d show higher cytotoxic activity than the parent compound icaritin against these cancer cell lines. Compounds 5b and 5d are even more cytotoxic to MCF-7 cells than the clinic drug tamoxifen. Moreover, compound 5b is found to be non-toxic to normal cells (Vero) and both 5b and 5d exhibit good selectivity towards estrogen receptor positive MCF-7 breast cancer cells over estrogen receptor negative MDA-MB-435s breast cancer cells. The structure activity relationship analysis has revealed that mono-substitution at either C-3 or C-7 hydroxyl group of icaritin could improve the cytotoxicity of icaritin, and the C-3 hydroxyl group may be a preferable site for chemical modification. In addition, the length, the flexibility and the additional branching substituent group of the substitution chain(s) at both C-3 and C-7 hydroxyl groups can all affect the anticancer activity of these derivatives. (C) 2015 Elsevier Masson SAS. All rights reserved.
• Semisynthetic Flavone-Derived Antimicrobials with Therapeutic Potential against Methicillin-Resistant<i>Staphylococcus aureus</i>(MRSA)
  作者：Shuimu Lin、Jun-Jie Koh、Thet Tun Aung、Wan Ling Wendy Sin、Fanghui Lim、Lin Wang、Rajamani Lakshminarayanan、Lei Zhou、Donald T. H. Tan、Derong Cao、Roger W. Beuerman、Li Ren、Shouping Liu

  DOI：10.1021/acs.jmedchem.7b00380

  日期：2017.7.27

  A new series of semisynthetic flavone-based small molecules mimicking antimicrobial peptides has been designed from natural icaritin to combat drug-resistant Gram-positive bacterial infections. Compound 6 containing two arginine residues exhibited excellent antibacterial activity against Gram-positive bacteria, including MRSA, and very low toxicity to mammalian cells, resulting in a high selectivity

  从天然icaritin设计了一系列新的基于半黄酮的模拟抗菌肽的小分子，以对抗耐药的革兰氏阳性细菌感染。含有两个精氨酸残基的化合物6对革兰氏阳性细菌（包括MRSA）表现出优异的抗菌活性，并且对哺乳动物细胞的毒性极低，因此与临床试验中的几种具有膜活性的抗生素相比，其选择性高达511以上。我们的数据首次表明，icaritin衍生物可有效杀死细菌。同时，这是第一项采用仿生策略来设计有效的基于黄酮的膜靶向抗菌剂的研究。6通过破坏细菌膜表现出快速的杀菌活性，可以规避细菌抗药性的发展。重要的是，6在由MRSA和金黄色葡萄球菌引起的角膜感染的小鼠模型中非常有效。