(3aR,12aR)-3a,12a-二氢-3a,4,6-三羟基-9-(3-羟基-3-甲基丁基)-5H-呋喃并[3',2':4,5]呋喃并[3,2-b]氧杂蒽-5-酮 | 55256-53-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: (3aR,12aR)-3a,12a-二氢-3a,4,6-三羟基-9-(3-羟基-3-甲基丁基)-5H-呋喃并[3',2':4,5]呋喃并[3,2-b]氧杂蒽-5-酮
• 英文名称: austocystin D
• 英文别名: (4R,8R)-2,4,18-trihydroxy-15-(3-hydroxy-3-methylbutyl)-7,9,13-trioxapentacyclo[10.8.0.03,10.04,8.014,19]icosa-1,3(10),5,11,14,16,18-heptaen-20-one
• CAS: 55256-53-6
• 化学式: C₂₂H₂₀O₈
• 分子量: 412.396
• InChiKey: VXTQFTUOAJRUDO-IFMALSPDSA-N

物化性质

• 熔点：
  115°C
• 沸点：
  453.31°C (rough estimate)
• 密度：
  1.2649 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  30
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  8

制备方法与用途

类别：有毒物品
毒性分级：高毒
急性毒性：口服-小鼠 LD50:300 毫克/公斤
可燃性危险特性：可燃；燃烧产生刺激烟雾
储运特性：通风、低温干燥；与库房食品原料分开存放
灭火剂：干粉、泡沫、沙土、二氧化碳、雾状水

反应信息

• 作为反应物：
  描述：

  (3aR,12aR)-3a,12a-二氢-3a,4,6-三羟基-9-(3-羟基-3-甲基丁基)-5H-呋喃并[3',2':4,5]呋喃并[3,2-b]氧杂蒽-5-酮 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 反应 16.0h， 以81%的产率得到(3aR,12aR)-3a,4,6-trihydroxy-9-(3-hydroxy-3-methylbutyl)-3,3a-dihydro-2H-furo[3',2':4,5]furo[3,2-b]xanthen-5(12aH)-one
  参考文献：
  名称：

  The Selectivity of Austocystin D Arises from Cell-Line-Specific Drug Activation by Cytochrome P450 Enzymes

  摘要：

  The natural product austocystin D was identified as a potent cytotoxic agent with in vivo antitumor acitivity and selectivity for cells expressing the multidrug resistance transporter MDRI. We sought to elucidate the mechanism of austocystin D's selective cytotoxic acitivity. Here we show that the selective cytotoxic action of austocystin. D arises from its selective activation by cytochrome P450 (CYP) enzymes in specific cancer cell lines, leading to induction of DNA damage in cells and in vitro. The potency and selectivity of austocystin D is lost upon inhibition of CYP activation and does not require MDRI expression or activity. Furthermore the pattern of cytotoxicity of austocystin D was distinct from doxorubicin and etoposide and unlike aflatoxin B(1) a compound that resembles austocystin D and is also activated by CYP enzymes to induce DNA damage. Theses results suggest that sustocystin D may be of clinical benefit for targeting or overcoming chemoresistance.

  DOI：

  10.1021/np100429s

文献信息

• The Selectivity of Austocystin D Arises from Cell-Line-Specific Drug Activation by Cytochrome P450 Enzymes
  作者：Kevin M. Marks、Eun Sun Park、Alexander Arefolov、Katie Russo、Keiko Ishihara、Jennifer E. Ring、Jon Clardy、Astrid S. Clarke、Henry E. Pelish

  DOI：10.1021/np100429s

  日期：2011.4.25

  The natural product austocystin D was identified as a potent cytotoxic agent with in vivo antitumor acitivity and selectivity for cells expressing the multidrug resistance transporter MDRI. We sought to elucidate the mechanism of austocystin D's selective cytotoxic acitivity. Here we show that the selective cytotoxic action of austocystin. D arises from its selective activation by cytochrome P450 (CYP) enzymes in specific cancer cell lines, leading to induction of DNA damage in cells and in vitro. The potency and selectivity of austocystin D is lost upon inhibition of CYP activation and does not require MDRI expression or activity. Furthermore the pattern of cytotoxicity of austocystin D was distinct from doxorubicin and etoposide and unlike aflatoxin B(1) a compound that resembles austocystin D and is also activated by CYP enzymes to induce DNA damage. Theses results suggest that sustocystin D may be of clinical benefit for targeting or overcoming chemoresistance.