brefeldin A 7-O-glutarate | 213415-34-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: brefeldin A 7-O-glutarate
• 英文别名: 5-[[(1R,2R,3E,7S,11E,13S,15S)-2-hydroxy-7-methyl-5-oxo-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-15-yl]oxy]-5-oxopentanoic acid
• CAS: 213415-34-0
• 化学式: C₂₁H₃₀O₇
• 分子量: 394.465
• InChiKey: HXHHXTKXCWAIQQ-KPAKZFSHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  110
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  brefeldin A 7-O-glutarate 在 2,6-二甲基吡啶 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 64.0h， 生成 brefeldin A 7-O-glutarylamidohexanol
  参考文献：
  名称：

  Synthesis and Anticancer Activity of Brefeldin A Ester Derivatives

  摘要：

  Ester derivatives of brefeldin A ( BFA) were synthesized to determine which of its two hydroxyl groups could be modified while still maintaining biological activity. The compounds were tested for antiproliferative activity in the National Cancer Institute's 60 cancer cell line screen. Monoderivatization at the C4 and C7 alcohols was tolerated, yielding biologically active compounds, whereas the analogues derivatized at both positions were the least active in the series. Molecular modeling of the analogues revealed that both the C4 and C7 derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. The Golgi-disruptive properties of the analogues were determined using fluorescence imaging assays. The BFA ester conjugates synthesized in this study were cytotoxic to cancer cells, and we have shown that the disruption of the Golgi complex is not necessary for cytotoxicity. The brefeldin A ester derivatives are potential anticancer agents.

  DOI：

  10.1021/jm0602817
• 作为产物：
  描述：

  戊二酸酐 、 布雷非德菌素 A 在 吡啶 作用下， 反应 36.0h， 以42%的产率得到brefeldin A 7-O-glutarate
  参考文献：
  名称：

  Design and Synthesis of Brefeldin A Sulfide Derivatives as Prodrug Candidates with Enhanced Aqueous Solubilities

  摘要：

  The addition of a variety of thiols to the alpha,beta-unsaturated lactone functionality present in brefeldin A has been carried out, and the resulting sulfides have been oxidized to the corresponding sulfoxides. These sulfoxides have the potential to undergo syn elimination to regenerate brefeldin A. The sulfoxides were more active than the sulfides as cytotoxic agents in a variety of human cancer cell cultures with the activities of the sulfoxides approaching that of brefeldin A itself. The cytotoxicities of the sulfoxides may be due to their conversion back to brefeldin A. The kinetics of sulfoxide elimination to form brefeldin A were studied in four cases, and the results indicate that substantial amounts of brefeldin A are likely to be generated during the cytotoxicity assays of the sulfoxide derivatives. Since the oxidation of sulfides to sulfoxides is a common metabolic reaction, the sulfides derived from brefeldin A can be considered as potential brefeldin A prodrugs. Several of the sulfide derivatives were determined to have enhanced aqueous solubilities relative to brefeldin A itself, A number of brefeldin A succinates, glutarates, oxidation products, and sulfone derivatives were also prepared and evaluated for cytotoxicity in dancer cell cultures. Some of the more active brefeldin A derivatives were tested in an in vivo animal model in which hollow fibers containing cancer cell cultures were implanted subcutaneously (SC) and intraperitoneally (IF), and the compounds were administered IP. Greater cytotoxic activity was observed at the SC site than at the IP site for the majority of these compounds, an observation which is consistent with the hypothesis that they are acting as brefeldin A prodrugs in vivo.

  DOI：

  10.1021/jm970746g

文献信息

• Design and Synthesis of Brefeldin A Sulfide Derivatives as Prodrug Candidates with Enhanced Aqueous Solubilities
  作者：Ankush B. Argade、Rajesh Devraj、Jeffrey A. Vroman、Rudiger D. Haugwitz、Melinda Hollingshead、Mark Cushman

  DOI：10.1021/jm970746g

  日期：1998.8.1

  The addition of a variety of thiols to the alpha,beta-unsaturated lactone functionality present in brefeldin A has been carried out, and the resulting sulfides have been oxidized to the corresponding sulfoxides. These sulfoxides have the potential to undergo syn elimination to regenerate brefeldin A. The sulfoxides were more active than the sulfides as cytotoxic agents in a variety of human cancer cell cultures with the activities of the sulfoxides approaching that of brefeldin A itself. The cytotoxicities of the sulfoxides may be due to their conversion back to brefeldin A. The kinetics of sulfoxide elimination to form brefeldin A were studied in four cases, and the results indicate that substantial amounts of brefeldin A are likely to be generated during the cytotoxicity assays of the sulfoxide derivatives. Since the oxidation of sulfides to sulfoxides is a common metabolic reaction, the sulfides derived from brefeldin A can be considered as potential brefeldin A prodrugs. Several of the sulfide derivatives were determined to have enhanced aqueous solubilities relative to brefeldin A itself, A number of brefeldin A succinates, glutarates, oxidation products, and sulfone derivatives were also prepared and evaluated for cytotoxicity in dancer cell cultures. Some of the more active brefeldin A derivatives were tested in an in vivo animal model in which hollow fibers containing cancer cell cultures were implanted subcutaneously (SC) and intraperitoneally (IF), and the compounds were administered IP. Greater cytotoxic activity was observed at the SC site than at the IP site for the majority of these compounds, an observation which is consistent with the hypothesis that they are acting as brefeldin A prodrugs in vivo.
• Synthesis and Anticancer Activity of Brefeldin A Ester Derivatives
  作者：Nwanne O. Anadu、V. Jo Davisson、Mark Cushman

  DOI：10.1021/jm0602817

  日期：2006.6.1

  Ester derivatives of brefeldin A ( BFA) were synthesized to determine which of its two hydroxyl groups could be modified while still maintaining biological activity. The compounds were tested for antiproliferative activity in the National Cancer Institute's 60 cancer cell line screen. Monoderivatization at the C4 and C7 alcohols was tolerated, yielding biologically active compounds, whereas the analogues derivatized at both positions were the least active in the series. Molecular modeling of the analogues revealed that both the C4 and C7 derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. The Golgi-disruptive properties of the analogues were determined using fluorescence imaging assays. The BFA ester conjugates synthesized in this study were cytotoxic to cancer cells, and we have shown that the disruption of the Golgi complex is not necessary for cytotoxicity. The brefeldin A ester derivatives are potential anticancer agents.