8,11-二羟基-4-(2-羟基乙基)-6-[2-(2-羟基乙基氨基)乙基氨基]-2,3-二氢-1H-萘并[3,2-h]喹喔啉-7,12-二酮 | 137132-70-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 蒽
• 中文名称: 8,11-二羟基-4-(2-羟基乙基)-6-[2-(2-羟基乙基氨基)乙基氨基]-2,3-二氢-1H-萘并[3,2-h]喹喔啉-7,12-二酮
• 中文别名: 米托蒽醌杂质D
• 英文名称: 8,11-dihydroxy-4-(2-hydroxyethyl)-6-[[2-[(2-hydroxyethyl)amino]ethyl]amino]-1,2,3,4,7,12-hexahydronaphtho-[2,3-f]-chinoxaline-7,12-dione
• 英文别名: 8,11-dihydroxy-4-(2-hydroxyethyl)-6-[[2-[(2-hydroxyethyl)amino]ethyl]amino]-1,2,3,4,7,12-hexahydronaphtho-[2,3-f]-quinoxaline-7,12-dione；mitoxantrone (2-hydroxyethyl)piperazine；8,11-Dihydroxy-4-(2-hydroxyethyl)-6-(2-(2-hydroxyethylamino)ethylamino)-1,2,3,4-tetrahydronaphtho[2,3-f]quinoxaline-7,12-dione；8,11-dihydroxy-4-(2-hydroxyethyl)-6-[2-(2-hydroxyethylamino)ethylamino]-2,3-dihydro-1H-naphtho[3,2-f]quinoxaline-7,12-dione
• CAS: 137132-70-8
• 化学式: C₂₂H₂₆N₄O₆
• 分子量: 442.472
• InChiKey: GJMHXLAWJIOZMT-UHFFFAOYSA-N

物化性质

• 熔点：
  175-179°C
• 沸点：
  843.2±65.0 °C(Predicted)
• 密度：
  1.473±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  154
• 氢给体数：
  7
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  novantrone 在 双氧水 、 horseradish peroxidase 作用下， 以 aq. acetate buffer 为溶剂， 反应 0.5h， 以85%的产率得到8,11-二羟基-4-(2-羟基乙基)-6-[2-(2-羟基乙基氨基)乙基氨基]-2,3-二氢-1H-萘并[3,2-h]喹喔啉-7,12-二酮
  参考文献：
  名称：

  米托蒽醌的萘喹喔啉代谢产物的心脏毒性比母体化合物低，在抗癌治疗中它可能是一种对心脏更安全的药物。

  摘要：

  米托蒽醌（MTX）是一种抗肿瘤药，用于治疗多种类型的癌症和多发性硬化症，其心脏毒性发生率很高。但是，对MTX心脏毒性的潜在机制了解甚少，并且几乎没有研究其代谢产物的潜在毒性。因此，这项工作旨在合成MTX-萘喹喔啉代谢物（NAPHT），并使用药理学相关浓度（0.01-5 µM）比较其在7天分化的H9c2细胞中对母体化合物的细胞毒性。在所有进行的细胞毒性测试[3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四氮唑还原，中性红吸收和乳酸脱氢酶释放测定]和测试时间中，MTX在同等浓度下的毒性更高。 24和48小时）。孵育12小时后，MTX和NAPHT在7天分化的H9c2细胞中均显着降低了线粒体膜电位。但是，MTX或NAPHT孵育后，能量途径以不同的方式受到影响。与MTX一起孵育24小时后，ATP增加而乳酸水平降低，而对于相同的孵育时间和浓度，NAPHT不会产生任何明显的影响。ATP合酶活性的

  DOI：

  10.1007/s00204-016-1839-z

文献信息

• Antineoplastic anthraquinones. II. Design and synthesis of 1,2-Heteroannelated anthraquinones
  作者：Pong Chang、Chia-Fu Chen

  DOI：10.1002/jhet.5570330227

  日期：1996.3

  of heterocycle-fused anthraquinones were designed by taking morindaparvin-A (2a) as the lead structure. The compounds we synthesized and tested for antineoplastic activity include 1,2-alkylenedioxyanthraquinone, naphtho [2,3-f]-quinoxaline-7,12-dione, anthra[1,2-d]imidazole-6,11-dione and naphtho[2,3-f]quinoxaline-7,12-dione derivatives. Most of the synthesized anthraquinones possessed various degrees

  基于“ 2-苯并萘型”结构模式假说，以morindaparvin-A（2a）为主导结构设计了许多杂环稠合蒽醌。我们合成并测试其抗肿瘤活性的化合物包括1,2-亚烷基二氧基蒽醌，萘并[2,3 - f ]-喹喔啉-7,12-二酮，蒽[1,2 - d ]咪唑-6,11-二酮和萘并[2，3 - f ]喹喔啉-7，12-二酮衍生物。大多数合成的蒽醌具有不同程度的抗癌活性。这些化合物之一是2-氯甲基-1 H-蒽[1,2- d ]咪唑-6,11-二酮（4b）对所有测试的人类癌细胞系均表现出细胞毒活性。
• A Facile Synthesis of A Naphtho[2,3-f]-Quinoxaline-7, 12-Dione From Mitoxantrone
  作者：Pong Chang

  DOI：10.1080/00397919608003814

  日期：1996.11

  A facile ring closure reaction of mitoxantrone for the preparation of naphtho[2,3-f]quinoxaline-7,12-dione 3a was studied and optimized. This method allows the preparation of 3a in multigram quantities without the need for chromatography.
• Oxidative metabolism of the anti-cancer agent mitoxantrone by horseradish, lacto-and lignin peroxidase
  作者：Thomas B. Brück、Dieter W. Brück

  DOI：10.1016/j.biochi.2010.09.015

  日期：2011.2

  Mitoxantrone (MH2X), an anthraquinone-type anti-cancer agent used clinically in the treatment of human malignancies, is oxidatively activated by the peroxidase/H2O2 enzyme system. In contrast to the enzymatic mechanisms of drug oxidation, the chemical transformations of MH2X are not well described. In this study, MH2X metabolites, produced by the horseradish, lacto- or lignin peroxidase (respectively HRP, LPO and LIP)/H2O2 system, were investigated by steady-state spectrokinetic and HPLC MS methods. At an equimolar mitoxantrone/H2O2 ratio, the efficacy of the enzyme-catalyzed oxidation of mitoxantrone decreased in the following order: LPO > HRP > LIP, which accorded with the decreasing size of the substrate access channel in the enzyme panel examined. In all cases, the central drug oxidation product was the redox-active cyclic metabolite, hexahydronaphtho-[2,3-f]-quinoxaline-7,12-dione (MH2), previously identified in the urine of mitoxantrone-treated patients. As the reaction progressed, data gathered in this study suggests that further oxidation of the MH2 side-chains occurred, yielding the mono- and dicarboxylic acid derivatives respectively. Based on the available data a further MH2 derivative is proposed, in which the amino-alkyl side-chain(s) are cyclised. With increasing H2O2 concentrations, these novel MH2 derivatives were oxidised to additional metabolites, whose spectral properties and MS data indicated a stepwise destruction of the MH2 chromophore due to an oxidative cleavage of the 9,10-anthracenedione moiety. The novel metabolites extend the known sequence of peroxidase-induced mitoxantrone metabolism, and may contribute to the cytotoxic effects of the drug in vivo. Based on the structural features of the proposed MH2 oxidation products we elaborate on various biochemical mechanisms, which extend the understanding of mitoxantrone's pharmaceutical action and its clinical effectiveness with a particular focus on peroxidase-expressing solid tumors, such as breast carcinoma. (C) 2010 Elsevier Masson SAS. All rights reserved.
• Reszka, Krzysztof J.; Chignell, Colin F., Molecular Pharmacology, 1996, vol. 50, # 6, p. 1612 - 1618
  作者：Reszka, Krzysztof J.、Chignell, Colin F.

  DOI：——

  日期：——
• Composition for Inhibiting or Preventing the Formation of a Biofilm
  申请人：Rossel Bart

  公开号：US20070258913A1

  公开（公告）日：2007-11-08

  Compounds for inhibiting and/or preventing the formation of a biofilm are disclosed. The compounds are an anthraquinone and/or a naphtoquinone, stereoisomeric forms, racemic mixtures, metabolites, esters or salts thereof, or mixtures thereof, and/or at least one plant extract including the compound or active fraction thereof. Compositions containing the compounds such as oral health products and methods of using the products in a method to prevent or inhibit biofilm formation are also disclosed. Preferred compositions include emodin and/or plant extracts from Rheum sp.