O⁷-benzyl glaziovianin A | 1252801-65-2

• 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: O⁷-benzyl glaziovianin A
• 英文别名: gatastatin；7-(Benzyloxy)-3-(4,7-dimethoxybenzo[D][1,3]dioxol-5-YL)-6-methoxy-4H-chromen-4-one；3-(4,7-dimethoxy-1,3-benzodioxol-5-yl)-6-methoxy-7-phenylmethoxychromen-4-one
• CAS: 1252801-65-2
• 化学式: C₂₆H₂₂O₈
• 分子量: 462.456
• InChiKey: XELFHZLMVXXOIT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4-二羟基-5-甲氧基苯乙酮 在 吡啶 、 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 、 碘 、 4-甲基苯磺酸吡啶 、 sodium carbonate 、 potassium carbonate 、 对甲苯磺酸 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 氯仿 、 水 、 乙腈 为溶剂， 反应 56.5h， 生成 O⁷-benzyl glaziovianin A
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of the analogues of glaziovianin A, a potent antitumor isoflavone

  摘要：

  Various analogues of glaziovianin A, an antitumor isoflavone, were synthesized, and their biological activities were evaluated. O-7-modified glaziovianin A showed strong cytotoxicity against HeLa S-3 cells. Compared to glaziovianin A, the O-7-benzyl and O-7-propargyl analogues were more cytotoxic against HeLa S-3 cells and more potent M-phase inhibitors. Furthermore, O-7-modified molecular probes of glaziovianin A were synthesized for biological studies. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.005

文献信息

• Design, synthesis, and biological evaluation of the analogues of glaziovianin A, a potent antitumor isoflavone
  作者：Ichiro Hayakawa、Akiyuki Ikedo、Takumi Chinen、Takeo Usui、Hideo Kigoshi

  DOI：10.1016/j.bmc.2012.08.005

  日期：2012.10

  Various analogues of glaziovianin A, an antitumor isoflavone, were synthesized, and their biological activities were evaluated. O-7-modified glaziovianin A showed strong cytotoxicity against HeLa S-3 cells. Compared to glaziovianin A, the O-7-benzyl and O-7-propargyl analogues were more cytotoxic against HeLa S-3 cells and more potent M-phase inhibitors. Furthermore, O-7-modified molecular probes of glaziovianin A were synthesized for biological studies. (C) 2012 Elsevier Ltd. All rights reserved.
• Structure–activity relationship study of glaziovianin A against cell cycle progression and spindle formation of HeLa S3 cells
  作者：Akiyuki Ikedo、Ichiro Hayakawa、Takeo Usui、Sayaka Kazami、Hiroyuki Osada、Hideo Kigoshi

  DOI：10.1016/j.bmcl.2010.07.111

  日期：2010.9

  Various derivatives of glaziovianin A, an antitumor isoflavone, were synthesized, and the cytotoxicity of each against HeLa S-3 cells was investigated. Compared to glaziovianin A, the O-7-allyl derivative was found to be more cytotoxic against HeLa S-3 cells and a more potent M-phase inhibitor. (c) 2010 Elsevier Ltd. All rights reserved.
• Structure Optimization of Gatastatin for the Development of γ-Tubulin-Specific Inhibitor
  作者：Kana Shintani、Haruna Ebisu、Minagi Mukaiyama、Taisei Hatanaka、Takumi Chinen、Daisuke Takao、Yoko Nagumo、Akira Sakakura、Ichiro Hayakawa、Takeo Usui

  DOI：10.1021/acsmedchemlett.9b00526

  日期：2020.6.11

  Gatastatin (O-7-benzyl glaziovianin A) is a gamma-tubulin-specific inhibitor that is used to investigate gamma-tubulin function in cells. We have previously reported that the unsubstituted phenyl ring of the O-7-benzyl group in gatastatin is important for gamma-tubulin inhibition. To obtain further structural information regarding gamma-tubulin inhibition, we synthesized several gatastatin derivatives containing a fixed O-7-benzyl moiety. Modifications of the B-ring resulted in drastic decrease in cytotoxicity, abnormal spindle formation activity, and inhibition of microtubule (MT) nucleation. In contrast, various O-6-alkylated gatastatin derivatives showed potent cytotoxicity, induced abnormal spindle formation, and inhibited MT nucleation. We had previously reported that O-6-benzyl glaziovianin A is a potent alpha/beta-tubulin inhibitor; thus, these new results suggest that the O-6-position restricts affinity for alpha/beta- and gamma-tubulin. Considering that an O-7-benzyl group increases specificity for gamma-tubulin, more potent and specific gamma-tubulin inhibitors can be generated through O-6-modifications of gatastatin.