combretastatin A4 disodium phosphate

• 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: combretastatin A4 disodium phosphate
• 英文别名: (Z)-2-methoxy-5-(3,4,5-trimethoxystyryl)phenyl disodium phosphate；disodium combretastatin A-4 3-O-phosphate；combretastatin A-4 disodium phosphate；combretastatin-A4-disodiumphosphate；combretastatin A4 phosphate；combretastatin A-4P；sodium;[2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] phosphate
• 化学式: C₁₈H₁₉O₈P*2Na
• 分子量: 440.297
• InChiKey: HRFFGGIUECGXRH-YSMBQZINSA-L

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  109
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  combretastatin A4 disodium phosphate 在 sodium azide 、 乙二胺四乙酸 作用下， 以 aq. buffer 为溶剂， 生成 combretastatin A4 disodium phosphate
  参考文献：
  名称：

  Concentration-Induced J-Aggregate Formation Causes a Biphasic Change in the Release of trans-Combretastatin A4 Disodium Phosphate from Archaeosomes and the Subsequent Cytotoxicity on Mammary Cancer Cells

  摘要：

  Combretastatin A4 disodium phosphate (CA4P) is a fluorescent, water-soluble prodrug able to induce vascular shutdown within tumors at doses less than one-tenth of the maximum tolerated dose. As a continued effort to develop efficient liposomal CA4P to treat solid tumor, we herein investigate the physical and spectroscopic properties of CA4P in aqueous solution and the mechanism of CA4P release from archaeal tetraether liposomes (archaeosomes). We found that cis-CA4P can be photoisomerized to trans-CA4P. This photoisomerization results in an increase in fluorescence intensity. Both cis- and trans-CA4P undergo fluorescence intensity self-quenching after they reach a critical concentration C-q (similar to 0.15-0.25 mM). Moreover, both cis- and trans-CA4P in buffer exhibit a red shift in their excitation spectrum and an increase in excitation spectrum band sharpness with increasing concentration, which can be attributed to the formation of J-aggregates. The onset of the dramatic change in excitation maximum occurs at concentrations close to Cq, suggesting that the self-quenching arises from extensive J-aggregate formation and that, when CA4P concentration exceeds Cq, J-aggregate formation begins to increase sharply. Our data also suggest that the extent of J-aggregate formation plays a critical role in CA4P release from tetraether archaeosomes and in the subsequent cytotoxicity on cultured human breast cancer MCF-7 cells. The drug leakage and cytotoxicity rate constants vary with the initial CA4P concentration entrapped inside archaeosomes in a biphasic manner, reaching a local maximum at 0.25-0.50 mM. A mechanism based on the concept of J-aggregate formation has been proposed to explain the biphasic changes in drug release and cytotoxicity with increasing drug concentration. Tetraether archaeosomes are extraordinarily stable and relatively nontoxic to animals; thus, they are promising nano drug carriers. The results obtained from this study pave the way for future development of archaeosomal CA4P to treat solid tumors.

  DOI：

  10.1021/acs.molpharmaceut.5b00500
• 作为产物：
  描述：

  康布瑞汀磷酸二钠 在 水 、 sodium hydroxide 作用下， 以 乙醇 为溶剂， 以1.2 g的产率得到combretastatin A4 disodium phosphate
  参考文献：
  名称：

  使用可再生生物质为基础的实用和绿色合成Combretastatin A-4及其前药CA4P

  摘要：

  描述了一种实用且绿色的方法，用于合成血管破坏剂康普他汀A-4（CA4）及其水溶性前药CA4P。从可从中国八角茴香（Illicium v​​erum Hook.f.）大量可持续获得的基于生物质的化合物茴香脑开始，可以在五个步骤中获得关键的中间体3-羟基-4-甲氧基苯基乙酸。该酸与另一种天然衍生的化合物3,4,5-三甲氧基苯甲醛之间进行珀金缩合，然后进行脱羧，从而制得康布雷他汀A-4，总收率良好。磷酸盐produrg CA4P可以在简单温和的条件下以连续的一锅两步反应制备。 康他汀A-4-康他汀A-4磷酸盐-可再生资源-绿色合成-珀金反应

  DOI：

  10.1055/s-0030-1258358

文献信息

• Combretastatin A-4 and Derivatives: Potential Fungicides Targeting Fungal Tubulin
  作者：Zhong-lin Ma、Xiao-jing Yan、Lei Zhao、Jiu-jiu Zhou、Wan Pang、Zhen-peng Kai、Fan-hong Wu

  DOI：10.1021/acs.jafc.5b05119

  日期：2016.2.3

  configuration and hydroxyl group in combretastatin A-4 are crucial to the antifungal effect. Molecular modeling indicated the binding sites of combretastatin A-4 and carbendazim on fungal tubulin are totally different. The bioactivity of combretastatin A-4 and its derivatives against carbendazim-resistant strains was demonstrated in this study. The results provide a new approach for fungicide discovery and

  Combretastatin A-4首先从非洲柳树Combretum caffrum中分离出来，是医学上的微管蛋白聚合抑制剂。在本研究中，它首先被假定为潜在的针对真菌微管蛋白的杀菌剂，可用于控制植物病害。合成了Combretastatin A-4及其衍生物，并对其进行了茄枯萎病和稻瘟病菌的抗药性试验。几种化合物的EC 50值类似于或优于异丙基硫烷的EC 50值，后者广泛用于水稻疾病控制。结构-活性关系研究表明顺式康他汀A-4的构型和羟基对于抗真菌作用至关重要。分子建模表明，康布雷他汀A-4和多菌灵在真菌微管蛋白上的结合位点完全不同。这项研究证明了康普他汀A-4及其衍生物对多菌灵耐药菌株的生物活性。结果为杀菌剂发现和杀菌剂抗性管理提供了一种新方法。