17-O-[N-(2-bromoethyl)carbamoyl]latrunculin A | 1017535-86-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: 17-O-[N-(2-bromoethyl)carbamoyl]latrunculin A
• 英文别名: [(1R,4Z,8E,10Z,12S,15R,17S)-5,12-dimethyl-3-oxo-17-[(4R)-2-oxo-1,3-thiazolidin-4-yl]-2,16-dioxabicyclo[13.3.1]nonadeca-4,8,10-trien-17-yl] N-(2-bromoethyl)carbamate
• CAS: 1017535-86-2
• 化学式: C₂₅H₃₅BrN₂O₆S
• 分子量: 571.533
• InChiKey: ZPHSMQHQJGJQEQ-ODVPECJOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-溴异氰酸乙酯 、 红海海绵素 A 在 三乙胺 作用下， 以 甲苯 为溶剂， 反应 1.0h， 以26.6%的产率得到17-O-[N-(2-bromoethyl)carbamoyl]latrunculin A
  参考文献：
  名称：

  Latrunculin A and Its C-17-O-Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells

  摘要：

  The marine-derived macrolides latrunculins A (1) and B, from the Red Sea sponge Negombata magnifica, have been found to reversibly bind actin monomers, forming a 1: 1 complex with G-actin and disrupting its polymerization. The microfilament protein actin is responsible for several essential functions within the cell such as cytokinesis and cell migration. One of the main binding pharmacophores of 1 to G-actin was identified as the C-17 lactol hydroxyl moiety that binds arginine 210 NH. Latrunculin A-17-O-carbamates 2-6 were prepared by reaction with the corresponding isocyanates. Latrunculin A (1) and carbamates 4-6 displayed potent anti-invasive activity against the human highly metastatic human prostate cancer PC-3M cells in a Matrigel assay at a concentration range of 50 nM to 1 mu M. Latrunculin A (1, 500 nM) decreased the disaggregation and cell migration of PC-3M-CT+ spheroids by 3-fold. Carbamates 4 and 5 were 2.5- and 5-fold more active than 1, respectively, in this assay with less actin binding affinity. Latrunculin A (1, IC50 6.7 mu M) and its 17-O-[N-(benzyl)carbamate (6, IC50 29 mu M) suppress hypoxia-induced HIF-1 activation in T47D breast tumor cells.

  DOI：

  10.1021/np070587w

文献信息

• Latrunculin A and Its C-17-<i>O</i>-Carbamates Inhibit Prostate Tumor Cell Invasion and HIF-1 Activation in Breast Tumor Cells
  作者：Khalid A. El Sayed、Mohammad A. Khanfar、Hassan M. Shallal、A. Muralidharan、Bhushan Awate、Diaa T. A. Youssef、Yang Liu、Yu-Dong Zhou、Dale G. Nagle、Girish Shah

  DOI：10.1021/np070587w

  日期：2008.3.1

  The marine-derived macrolides latrunculins A (1) and B, from the Red Sea sponge Negombata magnifica, have been found to reversibly bind actin monomers, forming a 1: 1 complex with G-actin and disrupting its polymerization. The microfilament protein actin is responsible for several essential functions within the cell such as cytokinesis and cell migration. One of the main binding pharmacophores of 1 to G-actin was identified as the C-17 lactol hydroxyl moiety that binds arginine 210 NH. Latrunculin A-17-O-carbamates 2-6 were prepared by reaction with the corresponding isocyanates. Latrunculin A (1) and carbamates 4-6 displayed potent anti-invasive activity against the human highly metastatic human prostate cancer PC-3M cells in a Matrigel assay at a concentration range of 50 nM to 1 mu M. Latrunculin A (1, 500 nM) decreased the disaggregation and cell migration of PC-3M-CT+ spheroids by 3-fold. Carbamates 4 and 5 were 2.5- and 5-fold more active than 1, respectively, in this assay with less actin binding affinity. Latrunculin A (1, IC50 6.7 mu M) and its 17-O-[N-(benzyl)carbamate (6, IC50 29 mu M) suppress hypoxia-induced HIF-1 activation in T47D breast tumor cells.