4-hydroxy-3, 4-seco-ursan-12-en-28-oic acid 3, 4 lactone | 1198208-30-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 4-hydroxy-3, 4-seco-ursan-12-en-28-oic acid 3, 4 lactone
• 英文别名: (1R,2S,5S,8R,9S,10S,14R,15R,21R)-1,2,8,9,15,20,20-heptamethyl-18-oxo-19-oxapentacyclo[12.9.0.02,11.05,10.015,21]tricos-11-ene-5-carboxylic acid
• CAS: 1198208-30-8
• 化学式: C₃₀H₄₆O₄
• 分子量: 470.693
• InChiKey: NFFBHRXPIVXYHH-OADIDDRXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  34
• 可旋转键数：
  1
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-hydroxy-3, 4-seco-ursan-12-en-28-oic acid 3, 4 lactone 在 potassium hydroxide 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以48%的产率得到3, 4-seco-Ursan-4-hydroxy-12-en-3, 28-dioic acid
  参考文献：
  名称：

  Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species

  摘要：

  Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives 5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco-structures prepared from 1 also showed the increase of the cytotoxicity against NTUB1 cells. Exposure of NTUB1 to 5 (40 mu M) and 23 (20 and 50 mu M) for 24 h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 mu M) and 23 (20 and 50 mu M) for 48 h also significantly increased the production of ROS while exposure of cells to 17 did not increase the amount of ROS. Flow cytometric analysis exhibited that treatment of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an increase in apoptotic cell death after 24 or 48 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h mediated through increased amount of ROS in cells exposed with 5 and 23, respectively, while the presence of G2/M arrest before accumulation of cells in sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in cells exposed with 5. The inhibition of tubulin polymerization and cell cycle arrest at G2/M following by apoptosis presented in the cell cycle of 23 also mediates through the increase amount of ROS induced by treating NTUB1 with 23 for 48 h. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.08.046
• 作为产物：
  描述：

  3-氧代-12-烯-28-乌苏酸 在 lithium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以8%的产率得到4-hydroxy-3, 4-seco-ursan-12-en-28-oic acid 3, 4 lactone
  参考文献：
  名称：

  Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors

  摘要：

  A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 mu M and 0.86 mu M respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry. Compounds D7 and D10 as well as B4, ring-A cleaved 3,30-dioic acid, also displayed remarkable inhibition on both HBV DNA replication at the concentration of 25 mu M and HBV cccDNA (covalently closed circularDNA) replication with IC50 values of 33.5 mu M, 32.7 mu M and 12.3 mu M respectively. (C) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2018.03.076

文献信息

• Ursolic acid derivatives induce cell cycle arrest and apoptosis in NTUB1 cells associated with reactive oxygen species
  作者：Huang-Yao Tu、A-Mei Huang、Bai-Luh Wei、Kim-Hong Gan、Tzyh-Chyuan Hour、Shyh-Chyun Yang、Yeong-Shiau Pu、Chun-Nan Lin

  DOI：10.1016/j.bmc.2009.08.046

  日期：2009.10

  Twenty-three ursolic acid (1) derivatives 2-24 including nine new 1 derivatives 5, 7-11, 20-22 were synthesized and evaluated for cytotoxicities against NTUB1 cells (human bladder cancer cell line). Compounds 5 and 17 with an isopropyl ester moiety at C-17-COOH and a succinyl moiety at C-3-OH showed potent inhibitory effect on growth of NTUB1 cells. Compounds 23 and 24 with seco-structures prepared from 1 also showed the increase of the cytotoxicity against NTUB1 cells. Exposure of NTUB1 to 5 (40 mu M) and 23 (20 and 50 mu M) for 24 h significantly increased the production of reactive oxygen species (ROS) while exposure of NTUB1 to 5 (20 and 40 mu M) and 23 (20 and 50 mu M) for 48 h also significantly increased the production of ROS while exposure of cells to 17 did not increase the amount of ROS. Flow cytometric analysis exhibited that treatment of NTUB1 with 5 or 17 or 23 led to the cell cycle arrest accompanied by an increase in apoptotic cell death after 24 or 48 h. These data suggest that the presentation of G1 phase arrest and apoptosis in 5- and 23-treated NTUB1 for 24 h mediated through increased amount of ROS in cells exposed with 5 and 23, respectively, while the presence of G2/M arrest before accumulation of cells in sub-G1 phase in 5-treated cells for 48 h also due to increased amount of ROS in cells exposed with 5. The inhibition of tubulin polymerization and cell cycle arrest at G2/M following by apoptosis presented in the cell cycle of 23 also mediates through the increase amount of ROS induced by treating NTUB1 with 23 for 48 h. (C) 2009 Elsevier Ltd. All rights reserved.
• Design, synthesis and biological evaluation of seco-A-pentacyclic triterpenoids-3,4-lactone as potent non-nucleoside HBV inhibitors
  作者：Zhijian Li、Qingxi Min、Haoji Huang、Ruixuan Liu、Yongyan Zhu、Quanhong Zhu

  DOI：10.1016/j.bmcl.2018.03.076

  日期：2018.5

  A series of seco-A-pentacyclic triterpenoids-3,4-lactone were synthesized and the anti-HBV activities were evaluated in vitro. Several compounds inhibited the secretion of HBV antigen and the replication of HBV DNA in micromolar level. Compounds D7 and D10, seco-A-oleanane-3,4-lactone, suppressed the HBeAg secretion with IC50 values of 0.14 mu M and 0.86 mu M respectively, and the inhibitory activities were also confirmed by detecting the fluorescence intensity of FITC-labeled monoclonal mouse HBeAg antibody via flow cytometry. Compounds D7 and D10 as well as B4, ring-A cleaved 3,30-dioic acid, also displayed remarkable inhibition on both HBV DNA replication at the concentration of 25 mu M and HBV cccDNA (covalently closed circularDNA) replication with IC50 values of 33.5 mu M, 32.7 mu M and 12.3 mu M respectively. (C) 2018 Elsevier Ltd. All rights reserved.