1,3-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-enyl)-9-oxo-9H-xanthen-6-yl diethylcarbamate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 1,3-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-enyl)-9-oxo-9H-xanthen-6-yl diethylcarbamate
• 英文别名: [6,8-dihydroxy-2-methoxy-1,7-bis(3-methylbut-2-enyl)-9-oxoxanthen-3-yl] N,N-diethylcarbamate
• 化学式: C₂₉H₃₅NO₇
• 分子量: 509.599
• InChiKey: BBFQKXKCZMZTMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  α-倒捻子素 、 N,N-二乙基氯甲酰胺 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以26%的产率得到1,3-dihydroxy-7-methoxy-2,8-bis(3-methylbut-2-enyl)-9-oxo-9H-xanthen-6-yl diethylcarbamate
  参考文献：
  名称：

  Discovery of α-mangostin as a novel competitive inhibitor against mutant isocitrate dehydrogenase-1

  摘要：

  Somatic heterozygous mutations of isocitrate dehydrogenase-1 (IDH1) are abundantly found in several types of cancer and strongly implicate altered metabolism in carcinogenesis. In the present study, we have identified alpha-mangostin as a novel selective inhibitor of mutant IDH1 (IDH1-R132H). We have observed that alpha-mangostin competitively inhibits the binding of alpha-ketoglutarate (alpha-KG) to IDH1-R132H. The structure-relationship study reveals that alpha-mangostin exhibits the strongest core inhibitor structure. Finally, we have observed that alpha-mangostin selectively promotes demethylation of 5-methylcytosine (5mC) and histone H3 trimethylated lysine residues in IDH1 (+/R132H) MCF10A cells, presumably via restoring the activity of cellular alpha-KG-dependent DNA hydroxylases and histone H3 lysine demethylases. Collectively, we provide evidence that alpha-mangostin selectively inhibits IDH1-R132H. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.10.034

文献信息

• Discovery of α-mangostin as a novel competitive inhibitor against mutant isocitrate dehydrogenase-1
  作者：Hyo-Joon Kim、Xiang Fei、Seok-Cheol Cho、Bu Young Choi、Hee-Chul Ahn、Kyeong Lee、Seung-Yong Seo、Young-Sam Keum

  DOI：10.1016/j.bmcl.2015.10.034

  日期：2015.12

  Somatic heterozygous mutations of isocitrate dehydrogenase-1 (IDH1) are abundantly found in several types of cancer and strongly implicate altered metabolism in carcinogenesis. In the present study, we have identified alpha-mangostin as a novel selective inhibitor of mutant IDH1 (IDH1-R132H). We have observed that alpha-mangostin competitively inhibits the binding of alpha-ketoglutarate (alpha-KG) to IDH1-R132H. The structure-relationship study reveals that alpha-mangostin exhibits the strongest core inhibitor structure. Finally, we have observed that alpha-mangostin selectively promotes demethylation of 5-methylcytosine (5mC) and histone H3 trimethylated lysine residues in IDH1 (+/R132H) MCF10A cells, presumably via restoring the activity of cellular alpha-KG-dependent DNA hydroxylases and histone H3 lysine demethylases. Collectively, we provide evidence that alpha-mangostin selectively inhibits IDH1-R132H. (C) 2015 Elsevier Ltd. All rights reserved.