棉子酚酛 | 4547-72-2

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 中文名称: 棉子酚酛
• 中文别名: 棉酚酮；6,6′,7,7′-四羟基-5,5′-二异丙基-3,3′-二甲基-(2,2′-联萘)-1,1′,4,4′-四酮-8,8′-二甲醛
• 英文名称: gossypolone
• 英文别名: 7-(8-formyl-6,7-dihydroxy-3-methyl-1,4-dioxo-5-propan-2-ylnaphthalen-2-yl)-2,3-dihydroxy-6-methyl-5,8-dioxo-4-propan-2-ylnaphthalene-1-carbaldehyde
• CAS: 4547-72-2
• 化学式: C₃₀H₂₆O₁₀
• 分子量: 546.53
• InChiKey: YSPBCFMMSKAENM-UHFFFAOYSA-N

物化性质

• 熔点：
  256-260 °C(Solv: acetic acid (64-19-7); water (7732-18-5))
• 沸点：
  842.1±65.0 °C(Predicted)
• 密度：
  1.485±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.47
• 重原子数：
  40.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  183.34
• 氢给体数：
  4.0
• 氢受体数：
  10.0

制备方法与用途

Gossypolone 是一种RNA结合蛋白Musashi-1抑制剂，其Ki值为12 nM。该化合物能够破坏Musashi与numb RNA之间的相互作用，并直接结合到MSI1蛋白的RBD1区域。因此，Gossypolone 在癌症研究中具有应用价值。

反应信息

• 作为反应物：
  描述：

  棉子酚酛 在 甲醇 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 24.25h， 生成 6,7,6',7'-tetrahydroxy-5,5'-diisopropyl-3,3'-dimethyl-8,8'-bis-phenylsulphanylmethyl-[2,2']binaphthalenyl-1,4,1',4'-tetraone
  参考文献：
  名称：

  GOSSYPOL DERIVATIVES, PRODUCTION METHOD THEREOF AND USES OF SAME

  摘要：

  本发明涉及一般式（1）的化合物：其中，独立于彼此的R1和R2代表：—OH，或—CH2—O—R3，或—CH2—S—R3，或R3，R4，R5和R6分别独立地代表—H或含有1至10个碳原子的含碳基团，饱和或不饱和，可选地取代一个或多个杂原子基团。本发明还涉及含有这些化合物的药物组合物及其用途，特别是在癌症治疗方面的应用。

  公开号：

  US20090318566A1
• 作为产物：
  描述：

  (-)-棉子素 在 三氯化铁 作用下， 以 溶剂黄146 、 丙酮 为溶剂， 以49%的产率得到棉子酚酛
  参考文献：
  名称：

  棉酚相关化合物的合成和细胞毒性。

  摘要：

  提取或合成了棉酚，棉酚，还原棉酚和外消旋棉酚和棉酚的新希夫碱。确定了它们对KB人癌细胞的细胞毒性活性。棉酚和棉酚的乙胺衍生物是活性最高的化合物（在两种情况下，IC（50）均在微摩尔范围内）。当在无血清的情况下进行测试时，棉酚和棉酚的细胞毒性增加，而在培养基中加入过氧化氢酶和甘露醇时，其细胞毒性降低。

  DOI：

  10.1016/s0223-5234(00)00165-3

文献信息

• 棉酚衍生物和它们的制备 ,在农药上的应用及 抗癌活性
  申请人：南开大学

  公开号：CN105884634B

  公开（公告）日：2019-06-04

  本发明涉及棉酚衍生物及其制备方法和在防治植物病毒、杀虫、杀菌和抗癌方面的应用，式中各基团的意义见说明书。本发明的棉酚衍生物表现出优异的抗植物病毒，杀菌活性，杀虫活性和抗癌活性。。
• Gossypolhemiquinone, a dimeric sesquiterpenoid identified in cotton (Gossypium)
  作者：Robert Stipanovic、Lorraine Puckhaber、James Frelichowski、Jesus Esquivel、John Westbrook、Mike O’Neil、Alois Bell、Michael Dowd、Kater Hake、Sara Duke

  DOI：10.1016/j.phytochem.2015.12.009

  日期：2016.2

  The report that the cotton leaf perforator, Bucculatrix thurberiella, is one of the few insect herbivores to attack Gossypium thurberi prompted an investigation of the terpenoids present in the leaves of this wild species of cotton. Members of Gossypium produce subepidermal pigment glands in their leaves that contain the dimeric sesquiterpenoid gossypol as well as other biosynthetically related terpenoids

  棉花叶片穿孔虫 Bucculatrix thurberiella 是少数攻击 Gossypium thurberi 的昆虫食草动物之一的报告促使人们对这种野生棉花品种的叶子中的萜类化合物进行调查。Gossypium 的成员在它们的叶子中产生表皮下色素腺体，其中包含二聚倍半萜类棉酚以及其他生物合成相关的萜类化合物。除了棉酚之外，在 D 基因组成员 G. thurberi 中还发现了一种以前未知的二聚倍半萜类化合物棉酚半醌 (GHQ)。随后发现棉属 D 基因组的其他成员含有这种化合物，但在商业棉花品种中未检测到 GHQ。当以人工饮食喂养 Helicoverpa zea 时，GHQ 延迟了化蛹天数，减少了蛹的重量，与对照饮食相比，成年期存活率小于或等于棉酚。然而，当与最高测试剂量的棉酚（0.18%；15.5:84.5 GHQ:棉酚）组合时，GHQ 对存活率和化蛹天数具有协同作用。由于棉酚具有抗癌活性，因此还评估了
• Cytotoxicity of enantiomers of gossypol Schiff’s bases and optical stability of gossypolone
  作者：Vi-Thuy Dao、Michael K Dowd、Marie-Thérèse Martin、Christiane Gaspard、Michel Mayer、Robert J Michelot

  DOI：10.1016/j.ejmech.2004.04.001

  日期：2004.7

  Schiff's bases of gossypol were prepared with chiral gossypol and ethylamine. As has been similarly observed among the gossypol enantiomers, the (-)-gossypol ethylimine was more active than either the (+)-gossypol ethylimine or the racemic gossypol ethylimine against KB and MCF7 cells. Gossypolone was also observed to be more toxic than gossypol against both cell lines. All of the gossypol products tested

  用手性棉酚和乙胺制备光学的希夫棉酚碱。如在棉酚对映异构体中类似地观察到的，（-）-棉酚乙基亚胺比（+）-棉酚乙基亚胺或外消旋棉酚乙基亚胺对KB和MCF7细胞的活性更高。还观察到棉酚对两种细胞系的毒性都比棉酚高。测试的所有棉酚产品均对MCF7 / ADR（抗阿德里亚氨酸）细胞具有可比的毒性。由于快速消旋作用，从手性棉酚生产手性棉酚的尝试失败了。此外，由R-（+）-2-氨基-3-苯基-1-丙醇形成的棉酚的席夫碱衍生物只能在降低的温度下分离，这表明棉酚席夫碱的光学稳定性不如棉酚席夫碱。
• Inhibitory Effects of Gossypol, Gossypolone, and Apogossypolone on a Collection of Economically Important Filamentous Fungi
  作者：Jay E. Mellon、Carlos A. Zelaya、Michael K. Dowd、Shannon B. Beltz、Maren A. Klich

  DOI：10.1021/jf2044394

  日期：2012.3.14

  Racemic gossypol and its related derivatives gossypolone and apogossypolone demonstrated significant growth inhibition against a diverse collection of filamentous fungi that included Aspergillus flavus, Aspergillus parasiticus, Aspergillus alliaceus, Aspergillus fumigatus, Fusarium graminearum, Fusarium moniliforme, Penicillium chrysogenum, Penicillium corylophilum, and Stachybotrys atra. The compounds were tested in a Czapek agar medium at a concentration of 100 mu g/mL. Racemic gossypol and apogossypolone inhibited growth by up to 95%, whereas gossypolone effected 100% growth inhibition in all fungal isolates tested except A. flavus. Growth inhibition was variable during the observed time period for all tested fungi capable of growth in these treatment conditions. Gossypolone demonstrated significant aflatoxin biosynthesis inhibition in A. flavus AFI3 (B-1, 76% inhibition). Apogossypolone was the most potent aflatoxin inhibitor, showing greater than 90% inhibition against A. flavus and greater than 65% inhibition against A. parasiticus (B-1, 67%; G(1), 68%). Gossypol was an ineffectual inhibitor of aflatoxin biosynthesis in both A. flavus and A. parasiticus. Both gossypol and apogossypolone demonstrated significant inhibition of ochratoxin A production (47%; 91%, respectively) in cultures of A. alliaceus.
• Chiral gossypol derivatives: Evaluation of their anticancer activity and molecular modeling
  作者：Long Zhang、Haixia Jiang、Xingxin Cao、Huiyun Zhao、Fan Wang、Yuxin Cui、Biao Jiang

  DOI：10.1016/j.ejmech.2009.04.025

  日期：2009.10

  To better use gossypol to find promising anticancer compounds, a series of new and known bis-Schiff base analogs of chiral gossypol were synthesized, and their anticancer activity on HeLa, U87 and M85 cells was tested. The results showed that through a simple chemical modification, less active (+)-gossypol could be converted into more active derivatives. When compared with (-)-gossypol, many more potent compounds that could be the promising anticancer agents were found, and some of them were more potent than the anticancer drug Cisplatin against all three cancer cell lines. By eliminating target functional groups, we observed that the major contributor to the anticancer activity of chiral gossypol seemed to be the phenolic groups, and not the aldehyde groups. Through comprehensive analysis of chiral gossypol analogs, the structure-activity relationships were elaborated. (C) 2009 Elsevier Masson SAS. All rights reserved.