UNBS-1450 | 676541-58-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: UNBS-1450
• 英文别名: 3SU2W2Hmg8；(1'S,2S,3'R,5'S,7'R,10'R,12'R,14'R,15'S,18'R,19'R,22'S,23'R)-10',22'-dihydroxy-14'-(hydroxymethyl)-7',18'-dimethyl-19'-(5-oxo-2H-furan-3-yl)spiro[1,3-thiazolidine-2,9'-4,6,11-trioxahexacyclo[12.11.0.03,12.05,10.015,23.018,22]pentacosane]-4-one
• CAS: 676541-58-5
• 化学式: C₃₁H₄₃NO₉S
• 分子量: 605.75
• InChiKey: GRINEMOQBRCRRY-DJHKYUSNSA-N

物化性质

• 沸点：
  863.0±65.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  42
• 可旋转键数：
  2
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  169
• 氢给体数：
  4
• 氢受体数：
  10

制备方法与用途

UNBS-1450是一种钠通道拮抗剂，由2''-氧代沃鲁沙林衍生而成的半合成卡酚内酯。它对多种癌症细胞表现出良好疗效，并且具有良好的选择性毒性。在低纳摩尔浓度下，UNBS-1450能够诱导细胞凋亡。其机制包括切割前半胱天冬酶8、9和3/7，降低抗凋亡Mcl-1的表达，募集促凋亡Bak和Bax蛋白，并抑制NF-κB反式激活，最终导致细胞死亡。

反应信息

• 作为反应物：
  描述：

  UNBS-1450 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 生成 [(1'S,2S,3'R,5'S,7'R,10'R,12'R,14'R,15'S,18'R,19'R,22'S,23'R)-10',22'-dihydroxy-7',18'-dimethyl-4-oxo-19'-(5-oxo-2H-furan-3-yl)spiro[1,3-thiazolidine-2,9'-4,6,11-trioxahexacyclo[12.11.0.03,12.05,10.015,23.018,22]pentacosane]-14'-yl]methyl 4-hydroxypentanoate
  参考文献：
  名称：

  Identification of a Novel Cardenolide (2‘ ‘-Oxovoruscharin) from Calotropis procera and the Hemisynthesis of Novel Derivatives Displaying Potent in Vitro Antitumor Activities and High in Vivo Tolerance:  Structure−Activity Relationship Analyses

  摘要：

  Analysis of the methanolic extract of Calotropis procera root barks enabled the identification of a novel cardenolide (2"-oxovoruscharin) to be made. Of the 27 compounds that we hemisynthesized, one (23) exhibited a very interesting profile with respect to its hemisynthetic chemical yield, its in vitro antitumor activity, its in vitro inhibitory influence on the Na+/K+-ATPase activity, and its in vivo tolerance. Compound 23 displayed in vitro antitumor activity on a panel of 57 human cancer cell lines similar to taxol, and higher than SN-38 (the active metabolite of irinotecan), two of the most potent drugs used in hospitals to combat cancer.

  DOI：

  10.1021/jm049405a
• 作为产物：
  描述：

  UNBS-1244 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以79%的产率得到UNBS-1450
  参考文献：
  名称：

  Identification of a Novel Cardenolide (2‘ ‘-Oxovoruscharin) from Calotropis procera and the Hemisynthesis of Novel Derivatives Displaying Potent in Vitro Antitumor Activities and High in Vivo Tolerance:  Structure−Activity Relationship Analyses

  摘要：

  Analysis of the methanolic extract of Calotropis procera root barks enabled the identification of a novel cardenolide (2"-oxovoruscharin) to be made. Of the 27 compounds that we hemisynthesized, one (23) exhibited a very interesting profile with respect to its hemisynthetic chemical yield, its in vitro antitumor activity, its in vitro inhibitory influence on the Na+/K+-ATPase activity, and its in vivo tolerance. Compound 23 displayed in vitro antitumor activity on a panel of 57 human cancer cell lines similar to taxol, and higher than SN-38 (the active metabolite of irinotecan), two of the most potent drugs used in hospitals to combat cancer.

  DOI：

  10.1021/jm049405a