brefeldin A seco-acid | 132684-66-3

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: brefeldin A seco-acid
• 英文别名: TX-1875；(2E,4R)-4-hydroxy-4-{(1R,2S,4S)-4-hydroxy-2-[(1E,6S)-6-hydroxyhept-1-en-1-yl]cyclopentyl}but-2-enoic acid；(E,4R)-4-hydroxy-4-[(1R,2S,4S)-4-hydroxy-2-[(E,6S)-6-hydroxyhept-1-enyl]cyclopentyl]but-2-enoic acid
• CAS: 132684-66-3
• 化学式: C₁₆H₂₆O₅
• 分子量: 298.379
• InChiKey: JFMRAARESGPLQF-KQPMLPITSA-N

物化性质

• 沸点：
  531.6±50.0 °C(Predicted)
• 密度：
  1.243±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  98
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 brefeldin A seco-acid 以 甲醇 、 乙醚 为溶剂， 反应 0.17h， 以80%的产率得到brefeldin A seco-acid methyl ester
  参考文献：
  名称：

  Elucidation of strict structural requirements of Brefeldin A as an inducer of differentiation and apoptosis

  摘要：

  Brefeldin A (BFA) can induce a wide variety of human cancer cells to differentiation and apoptosis and is in development as an anticancer agent. To elucidate structural requirements for cytotoxicity and induction of differentiation and apoptosis, BFA was structurally modified into various derivatives including 4-epi-BFA in this study. Their inducing activities of apoptosis were evaluated with their cytotoxicities, DNA fragmentation and morphological changes in human colon cancer cell HCT 116. The cytotoxicity of 4-epi-BFA (TX-1923) (IC50 = 60 mu M) was 300 times lower than that of BFA (IC50 = 0.2 mu M). Furthermore, 4-epi-BFA induced DNA fragmentation and apoptotic morphological changes at much higher concentrations (70 and 50 mu M, respectively) than BFA (0.11 and 0.36 mu M, respectively). These results indicated that the configuration of 4-hydroxyl group of brefeldin A plays a key role in the cytotoxicity and induction of apoptosis. On the other hand, 7-O-acetyl-BFA, 4-O-acetyl-BFA, and 4,7-di-O-acetyl-BFA exhibited potential activities in cytotoxicity and inducibility of apoptosis. We suggested that the structural determinants for BFA include the moiety of the Michael acceptor, the conformational rigidity of the 13-membered ring, and the configuration of 4-hydroxyl group. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00297-7
• 作为产物：
  描述：

  布雷非德菌素 A 在 氢氧化钾 作用下， 反应 1.0h， 以90%的产率得到brefeldin A seco-acid
  参考文献：
  名称：

  Elucidation of strict structural requirements of Brefeldin A as an inducer of differentiation and apoptosis

  摘要：

  Brefeldin A (BFA) can induce a wide variety of human cancer cells to differentiation and apoptosis and is in development as an anticancer agent. To elucidate structural requirements for cytotoxicity and induction of differentiation and apoptosis, BFA was structurally modified into various derivatives including 4-epi-BFA in this study. Their inducing activities of apoptosis were evaluated with their cytotoxicities, DNA fragmentation and morphological changes in human colon cancer cell HCT 116. The cytotoxicity of 4-epi-BFA (TX-1923) (IC50 = 60 mu M) was 300 times lower than that of BFA (IC50 = 0.2 mu M). Furthermore, 4-epi-BFA induced DNA fragmentation and apoptotic morphological changes at much higher concentrations (70 and 50 mu M, respectively) than BFA (0.11 and 0.36 mu M, respectively). These results indicated that the configuration of 4-hydroxyl group of brefeldin A plays a key role in the cytotoxicity and induction of apoptosis. On the other hand, 7-O-acetyl-BFA, 4-O-acetyl-BFA, and 4,7-di-O-acetyl-BFA exhibited potential activities in cytotoxicity and inducibility of apoptosis. We suggested that the structural determinants for BFA include the moiety of the Michael acceptor, the conformational rigidity of the 13-membered ring, and the configuration of 4-hydroxyl group. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00297-7

文献信息

• Synthesis and activity of brefeldin a analogs as inducers of cancer cell differentiation and apoptosis
  作者：Ji-Wen Zhu、Hitoshi Hori、Hisao Nojiri、Takahiko Tsukuda、Zenei Taira

  DOI：10.1016/s0960-894x(96)00588-4

  日期：1997.1

  We designed and synthesized several brefeldin A (BFA) analogs. These compounds were evaluated for the ability to induce differentiation and apoptosis in human colonic carcinoma cell line HCT116. Diacetyl BFA (2a), 4-acetyl BFA (2b), 7-acetyl BFA (2c), and 10,11-epoxy BFA (3b) were active but tetrahydro BFA (3a) and other analogs could not induce the malignant cells to differentiate. The results suggested that the moiety from 1- to 4-position in BFA as well as its conformational rigidity is essential for its biological activity. (C) 1997, Elsevier Science Ltd.
• Elucidation of strict structural requirements of Brefeldin A as an inducer of differentiation and apoptosis
  作者：Ji-Wen Zhu、Hideko Nagasawa、Fumi Nagura、Saharuddin B Mohamad、Yoshihiro Uto、Kazuto Ohkura、Hitoshi Hori

  DOI：10.1016/s0968-0896(99)00297-7

  日期：2000.2

  Brefeldin A (BFA) can induce a wide variety of human cancer cells to differentiation and apoptosis and is in development as an anticancer agent. To elucidate structural requirements for cytotoxicity and induction of differentiation and apoptosis, BFA was structurally modified into various derivatives including 4-epi-BFA in this study. Their inducing activities of apoptosis were evaluated with their cytotoxicities, DNA fragmentation and morphological changes in human colon cancer cell HCT 116. The cytotoxicity of 4-epi-BFA (TX-1923) (IC50 = 60 mu M) was 300 times lower than that of BFA (IC50 = 0.2 mu M). Furthermore, 4-epi-BFA induced DNA fragmentation and apoptotic morphological changes at much higher concentrations (70 and 50 mu M, respectively) than BFA (0.11 and 0.36 mu M, respectively). These results indicated that the configuration of 4-hydroxyl group of brefeldin A plays a key role in the cytotoxicity and induction of apoptosis. On the other hand, 7-O-acetyl-BFA, 4-O-acetyl-BFA, and 4,7-di-O-acetyl-BFA exhibited potential activities in cytotoxicity and inducibility of apoptosis. We suggested that the structural determinants for BFA include the moiety of the Michael acceptor, the conformational rigidity of the 13-membered ring, and the configuration of 4-hydroxyl group. (C) 2000 Elsevier Science Ltd. All rights reserved.