(1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-1,2,6a,6b,9,9,12a-heptamethyl-10-(3-methylbutanoyloxy)-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid

• 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
• 英文名称: (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-1,2,6a,6b,9,9,12a-heptamethyl-10-(3-methylbutanoyloxy)-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
• 化学式: C₃₅H₅₆O₄
• 分子量: 540.827
• InChiKey: MAQWNYLCDKHCPQ-SKHUFZRLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.2
• 重原子数：
  39
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  异戊酸酐 、 熊果酸 在 4-二甲氨基吡啶 作用下， 以 吡啶 为溶剂， 生成 (1S,2R,4aS,6aR,6aS,6bR,8aR,10S,12aR,14bS)-1,2,6a,6b,9,9,12a-heptamethyl-10-(3-methylbutanoyloxy)-2,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydro-1H-picene-4a-carboxylic acid
  参考文献：
  名称：

  Anti-AIDS Agents 38. Anti-HIV Activity of 3-O-Acyl Ursolic Acid Derivatives

  摘要：

  Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC50 < 0.00035 and 0.00086 M; therapeutic index (TI) > 20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC50 4.4 muM) with oleanolic acid (EC50 3.7 muM), although it was slightly toxic (IC50 14.3 CIM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC50 of 0.31 muM and a TI of 155.5. In contrast, 3-O-(3',3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC50 2.1 muM, TI 23.6).

  DOI：

  10.1021/np990633v

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.
• Anti-AIDS Agents 38. Anti-HIV Activity of 3-<i>O</i>-Acyl Ursolic Acid Derivatives
  作者：Yoshiki Kashiwada、Tsuneatsu Nagao、Ayumi Hashimoto、Yasumasa Ikeshiro、Hikaru Okabe、L. Mark Cosentino、Kuo-Hsiung Lee

  DOI：10.1021/np990633v

  日期：2000.12.1

  Based on our previous finding that 3-O-acyl-betulinic and -oleanolic acids, especially the 3-O-(3',3'-dimethyl)-succinyl derivatives (2 and 4), demonstrated potent anti-HIV activity [EC50 < 0.00035 and 0.00086 M; therapeutic index (TI) > 20 000 and 22 326, respectively], several 3-O-acyl-ursolic acids were prepared and evaluated for anti-HIV activity. Ursolic acid (6) was equipotent (EC50 4.4 muM) with oleanolic acid (EC50 3.7 muM), although it was slightly toxic (IC50 14.3 CIM, TI 3.3). 3-O-Diglycoryl-ursolic acid (10) demonstrated relatively potent anti-HIV activity with an EC50 of 0.31 muM and a TI of 155.5. In contrast, 3-O-(3',3'-dimethylsuccinyl)-ursolic acid (8), which is analogous to the extremely potent anti-HIV betulinic acid and oleanolic acid derivatives 2 and 4, displayed only weak anti-HIV activity (EC50 2.1 muM, TI 23.6).