(22β)-(Z)-26-(4-nitrobenzylidene)-3β-hydroxy-furost-5-en 3-O-acetate | 1620908-07-7

• 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: (22β)-(Z)-26-(4-nitrobenzylidene)-3β-hydroxy-furost-5-en 3-O-acetate
• 英文别名: (Z)-26-(4-nitrobenzylidene)-furost-5en-3β-acetate
• CAS: 1620908-07-7
• 化学式: C₃₆H₄₉NO₅
• 分子量: 575.789
• InChiKey: JYVPQUPXPPBPDM-KZLPNFTASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.55
• 重原子数：
  42.0
• 可旋转键数：
  7.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  78.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为产物：
  描述：

  薯蓣皂素 在 吡啶 、 sodium hydride 、 sodium cyanoborohydride 、 溶剂黄146 、 pyridinium chlorochromate 作用下， 以 二氯甲烷 、 氯仿 、 甲苯 为溶剂， 反应 10.33h， 生成 (22β)-(Z)-26-(4-nitrobenzylidene)-3β-hydroxy-furost-5-en 3-O-acetate
  参考文献：
  名称：

  Synthesis of diosgenin analogues as potential anti-inflammatory agents

  摘要：

  We herein report the synthesis of diosgenin analogues from commercially available diosgenin as the starting material. The structures of newly synthesised compounds were confirmed by (1)H NMR, (13)C NMR and mass spectrometry. All analogues were evaluated for in-vitro anti-inflammatory profile against LPS-induced inflammation in primary peritoneal macrophages isolated from mice by quantification of pro-inflammatory (TNF-α, IL-6 and IL-1β) cytokines in cell culture supernatant using the ELISA technique followed by in-vitro cytotoxicity study. Among the synthesised analogues, analogue 15 [(E) 26-(3',4',5'-trimethoxybenzylidene)-furost-5en-3β-acetate)] showed significant anti-inflammatory activity by inhibiting LPS-induced pro-inflammatory cytokines in a dose-dependent manner without any cytotoxicity. Efficacy and safety of analogue 15 were further validated in an in-vivo system using LPS-induced sepsis model and acute oral toxicity in mice. Oral administration of analogue 15 inhibited the pro-inflammatory cytokines in serum, attenuated the liver and lung injury and reduced the mortality rate in sepsis mice. Acute oral toxicity study showed that analogue 15 is non-toxic at higher dose in BALB/c mice. Molecular docking study revealed the strong binding affinity of diosgenin analogues to the active site of the pro-inflammatory proteins. These findings suggested that analogue 15 may be a useful therapeutic candidate for the treatment of inflammatory diseases.

  DOI：

  10.1016/j.jsbmb.2014.04.006

文献信息

• Synthesis of novel anticancer agents through opening of spiroacetal ring of diosgenin
  作者：A.A. Hamid、Mohammad Hasanain、Arjun Singh、Balakishan Bhukya、Omprakash、Prema G. Vasudev、Jayanta Sarkar、Debabrata Chanda、Feroz Khan、O.O. Aiyelaagbe、Arvind S. Negi

  DOI：10.1016/j.steroids.2014.05.025

  日期：2014.9

  Diosgenin has been modified to furostane derivatives after opening the F-spiroacetal ring. The aldehyde group at C26 in derivative 8 was unexpectedly transformed to the ketone 9. The structure of ketone 9 was confirmed by spectroscopy and finally by X-ray crystallography. Five of the diosgenin derivatives showed significant anticancer activity against human cancer cell lines. The most potent molecule of this series i.e. compound 7, inhibited cellular growth by arresting the population at G0/G1 phase of cell division cycle. Cells undergo apoptosis after exposure to the derivative 7 which was evident by increase in sub G0 population in cell cycle analysis. Docking experiments showed caspase-3 and caspase-9 as possible molecular targets for these compounds. This was further validated by cleavage of PARP, a caspase target in apoptotic pathway. Compound 7 was found non-toxic up to 1000mg/kg dose in acute oral toxicity in Swiss albino mice.