brefeldin A 4,7-O-dibenzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: brefeldin A 4,7-O-dibenzoate
• 英文别名: [(1R,2R,3E,7S,11E,13S,15S)-2-benzoyloxy-7-methyl-5-oxo-6-oxabicyclo[11.3.0]hexadeca-3,11-dien-15-yl] benzoate
• 化学式: C₃₀H₃₂O₆
• 分子量: 488.58
• InChiKey: AQDVDHFGRQUIPI-WDGJUNTBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 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-dibenzoate
  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

• Semi-Synthesis, Cytotoxic Evaluation, and Structure—Activity Relationships of Brefeldin A Derivatives with Antileukemia Activity
  作者：Xu-Xiu Lu、Yao-Yao Jiang、Yan-Wei Wu、Guang-Ying Chen、Chang-Lun Shao、Yu-Cheng Gu、Ming Liu、Mei-Yan Wei

  DOI：10.3390/md20010026

  日期：——

  were characterized by spectroscopic methods. Their cytotoxic activities were evaluated against human chronic myelogenous leukemia K562 cell line in vitro, and the preliminary structure–activity relationships revealed that the hydroxy group played an important role. Moreover, the monoester derivatives exhibited stronger cytotoxic activity than the diester derivatives. Among them, brefeldin A 7-O-2-chloro-4

  Brefeldin A ( 1 ) 是一种有效的细胞毒性天然大环内酯，由海洋真菌青霉产生。 (HS-N-29) 来自药用红树Acanthus ilicifolius 。设计并半合成了其系列酯衍生物2 ~ 16 ，并通过光谱方法对其结构进行了表征。在体外评估了它们对人慢性粒细胞白血病 K562 细胞系的细胞毒活性，初步的构效关系表明羟基发挥了重要作用。此外，单酯衍生物比二酯衍生物表现出更强的细胞毒活性。其中布雷菲德菌素A 7- O -2-氯-4,5-二氟苯甲酸酯( 7 )对K562细胞增殖的抑制作用最强，IC 50值为0.84 µM。进一步的评估表明7诱导细胞周期停滞，刺激细胞凋亡，抑制BCR-ABL的磷酸化，从而失活其下游AKT信号通路。 AKT通路中下游信号分子的表达，包括mTOR和p70S6K，在7-处理后也以剂量依赖性方式减弱。此外，对接到 ARF1-GDP-GEF 复合物1 个结合