brefeldin A 4,7-O-di(1-naphthoate)

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: brefeldin A 4,7-O-di(1-naphthoate)
• 英文别名: [(1R,2R,3E,7S,11E,13S,15S)-7-methyl-2-(naphthalene-1-carbonyloxy)-5-oxo-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-15-yl] naphthalene-1-carboxylate
• 化学式: C₃₈H₃₆O₆
• 分子量: 588.7
• InChiKey: CNSUWVZCXIZQFE-PWEFIWIMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9
• 重原子数：
  44
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  78.9
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  brefeldin A 7-O-nicotinate 在 4-二甲氨基吡啶 、 水 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 aq. phosphate buffer 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 64.0h， 生成 brefeldin A 4,7-O-di(1-naphthoate)
  参考文献：
  名称：

  Synthesis and Cytotoxic Evaluation of Acylated Brefeldin A Derivatives as Potential Anticancer Agents

  摘要：

  Brefeldin A has attracted considerable attention because of its potential function in cancer prevention. However, its therapeutic use is limited by its poor bioavailability. The modifications on brefeldin A were difficult because of its low stability and selectivity toward two hydroxyl groups within the same molecule. In this study, we report the selective acylation of brefeldin A under mild conditions and the preparation of a series of monoacylated and diacylated brefeldin A derivatives. Their cytotoxicity, antitumor activity against TE‐1 cell, and molecular properties of adsorption, distribution, metabolism, and elimination were evaluated. Brefeldin A 7‐O‐benzoate, brefeldin A 4,7‐O‐dibenzoate, and brefeldin A 7‐O‐biotin carboxylate showed the most potent cytotoxic activity, with GI50 values of 0.39, 0.46, and 0.50 μm, respectively. Molecular docking of these analogs revealed that the derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. Our results may serve as a basis for the development of novel potential anticancer agents from brefeldin A derivatives.

  DOI：

  10.1111/cbdd.12154

文献信息

• Synthesis and Cytotoxic Evaluation of Acylated Brefeldin A Derivatives as Potential Anticancer Agents
  作者：Bingyong He、Yajun Wang、Yuguo Zheng、Wei Chen、Qing Zhu

  DOI：10.1111/cbdd.12154

  日期：2013.9

  Brefeldin A has attracted considerable attention because of its potential function in cancer prevention. However, its therapeutic use is limited by its poor bioavailability. The modifications on brefeldin A were difficult because of its low stability and selectivity toward two hydroxyl groups within the same molecule. In this study, we report the selective acylation of brefeldin A under mild conditions and the preparation of a series of monoacylated and diacylated brefeldin A derivatives. Their cytotoxicity, antitumor activity against TE‐1 cell, and molecular properties of adsorption, distribution, metabolism, and elimination were evaluated. Brefeldin A 7‐O‐benzoate, brefeldin A 4,7‐O‐dibenzoate, and brefeldin A 7‐O‐biotin carboxylate showed the most potent cytotoxic activity, with GI50 values of 0.39, 0.46, and 0.50 μm, respectively. Molecular docking of these analogs revealed that the derivatives were well tolerated at the interface between ARF1 and its guanine nucleotide exchange factor ARNO. Our results may serve as a basis for the development of novel potential anticancer agents from brefeldin A derivatives.