6,7-dichloro-2,5,8-trihydroxy-3-methyl-1,4-naphthoquinone

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6,7-dichloro-2,5,8-trihydroxy-3-methyl-1,4-naphthoquinone
• 英文别名: 2,3-Dichloro-5,6,8-trihydroxy-7-methylnaphthalene-1,4-dione；2,3-dichloro-5,6,8-trihydroxy-7-methylnaphthalene-1,4-dione
• 化学式: C₁₁H₆Cl₂O₅
• 分子量: 289.072
• InChiKey: VPFGQTGXNJSBKO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6,7-dichloro-2,5,8-trihydroxy-3-methyl-1,4-naphthoquinone 在 铁粉 、 氧气 作用下， 以 溶剂黄146 、 sodium hydroxide 为溶剂， 反应 0.33h， 以80%的产率得到3-hidroxi-2-metilnaftazarina
  参考文献：
  名称：

  卤代萘甲素和醌茜素的还原脱卤是制备母体化合物的简单途径

  摘要：

  摘要 通过 2-氯-3-烷基-、2,3-二氯（二溴）-、三氯-（三溴）-和四氯（四溴）-萘并和 2,3-二氯喹吖啶与 Fe/HOAc 反应，然后氧化在温和碱性条件下的空气中，以良好至极好的收率获得了相应的萘并芴素。

  DOI：

  10.1080/00397919808007029
• 作为产物：
  描述：

  2,3,6-trimethoxytoluene 、 2,3-二氯马来酸酐 、 三氯化铝 、 氯化钠 生成 6,7-dichloro-2,5,8-trihydroxy-3-methyl-1,4-naphthoquinone
  参考文献：
  名称：

  ANUFRIEV, V. F.;BALANEVA, N. N.;CHIZHOVA, A. YA.;NOVIKOV, V. L.;ELYAKOV, +, TIXOOKEAN. IN-T BIOORGAN. XIMII DALNEVOST. OTD-NIYA AN CCCP, VLADIVOSTOK,+

  摘要：

  DOI：

文献信息

• Fluoride salts-alcohols-alumina as reagents for nucleophilic substitution of chlorine atoms for alkoxy groups in 2,3-dichlorosubstituted juglones, naphthazarines, and quinizarines
  作者：Victor Ph. Anufriev、Vyacheslav L. Novikov

  DOI：10.1016/0040-4039(95)00295-n

  日期：1995.4

  Direct displacement of chlorine atoms by alkoxy groups in 2,3-dichlorosubstituted juglones (5-hydroxy-1,4-naphthoquinones), naphthazarines (5,8-dihydroxy-1,4-naphthoquinones), and quinizarines (1,4-dihydroxy-9,10-anthraquinones) is generally ineffective, however high yields are obtained when methanol or cellosolves activated by fluoride anion are used as nucleophiles and the reaction goes in the presence

  2,3-二氯取代的聚对二甲苯（5-羟基-1,4-萘醌），萘萘烷（5,8-二羟基-1,4-萘醌）和喹唑啉（1,4-二羟基）中的烷氧基直接取代氯原子（-9，10-蒽醌）通常无效，但是当将甲醇或由氟阴离子活化的溶纤剂用作亲核试剂并且反应在氧化铝的存在下进行时，可获得高产率。
• Activity of New Synthetic (2-Chloroethylthio)-1,4-naphthoquinones in Prostate Cancer Cells
  作者：Sergey A. Dyshlovoy、Dmitry N. Pelageev、Lea S. Jakob、Ksenia L. Borisova、Jessica Hauschild、Tobias Busenbender、Moritz Kaune、Ekaterina A. Khmelevskaya、Markus Graefen、Carsten Bokemeyer、Victor Ph. Anufriev、Gunhild von Amsberg

  DOI：10.3390/ph14100949

  日期：——

  Development of resistance to currently available standard therapies in advanced prostate cancer (PCa) emphasizes the need for novel therapeutic options. Here, we report the synthesis of new hybrid molecules consisting of 2-chloroethylthio and 1,4-naphthoquinone pharmacophores and describe their activity in PCa. In screening analyses, the introduction of one 2-chloroethylthio group improved the anticancer properties of 1,4-naphthoquinones, whereas the introduction of a second 2-chloroethylthio moiety rather decreased activity. Two most promising of the synthesized compounds, 30 and 32, were highly active in different human PCa cell lines harboring varying resistance profiles at nanomolar concentrations. The generated data suggest that the compounds are capable of mitochondria targeting, cytotoxic ROS induction, and DNA damage, which resulted in apoptosis presumably executed in a caspase-dependent manner. The substances synergized with the clinically approved PARP inhibitor olaparib and resensitized AR-V7-expressing PCa cells to antiandrogen enzalutamide, as well as to a combination of enzalutamide and an AKT inhibitor. This was at least in part exerted via down-regulation of AR-V7 expression and inhibition of AR signaling. Mild antagonism was observed in combination with platinum- or taxane-based chemotherapy, which was putatively related to treatment-induced activation of p38, JNK1/2, ERK1/2, MEK1/2, and AKT, functioning as potential pro-survival factors. Thus, the synthesized (2-chloroethylthio)-1,4-naphthoquinone derivatives exhibit promising anticancer properties in vitro, suggesting their further development as potential therapeutics for the treatment of castration-resistant PCa.

  目前，晚期前列腺癌（PCa）对现有标准疗法的耐药性的发展强调了新型治疗选择的必要性。在这里，我们报道了2-氯乙基硫和1,4-萘醌药效团组成的新型杂化分子的合成，并描述了它们在PCa中的活性。在筛选分析中，引入一个2-氯乙基硫基团改善了1,4-萘醌的抗癌性能，而引入第二个2-氯乙基硫基团则降低了活性。合成的两个最有前途的化合物30和32，在不同人类PCa细胞系中具有高活性，这些细胞系具有不同的耐药谱，浓度为纳摩尔级。生成的数据表明，这些化合物能够靶向线粒体，诱导细胞毒性ROS和DNA损伤，导致凋亡，可能是以caspase依赖的方式执行的。这些物质与临床批准的PARP抑制剂olaPARib协同作用，并使表达AR-V7的PCa细胞重新对抗雄激素受体拮抗剂恩扎鲁胺以及恩扎鲁胺和AKT抑制剂的联合治疗产生敏感性。这至少部分是通过下调AR-V7表达和抑制AR信号传导来发挥作用的。与铂类或紫杉醇类化疗的联合治疗中观察到轻度的拮抗作用，这可能与治疗引起的p38、JNK1/2、ERK1/2、MEK1/2和AKT的潜在促生存因子的活化有关。因此，合成的（2-氯乙基硫基）-1,4-萘醌衍生物在体外展示了有前途的抗癌性能，建议将其进一步开发为治疗去势抵抗性PCa的潜在治疗药物。
• A simple synthesis of natural spinazarins and their analogues
  作者：Dmitry N. Pelageev、Ksenia L. Borisova、Svetlana M. Kovach、Vyacheslav V. Makhankov、Victor Ph. Anufriev

  DOI：10.1016/j.mencom.2023.02.026

  日期：2023.3

  simple synthesis of spinazarins (2,3-dihydroxy-naphthazarins or 2,3,5,8-tetrahydroxy-1,4-naphtho-quinones) from available 2,3-dichloronaphthazarin derivatives involves replacement of chlorine atoms with azido groups followed by their acidic hydrolysis. The procedure can be used for the preparative synthesis of natural biologically active spinazarins and their analogues.

  从可用的 2,3-二氯萘并衍生物中简单合成 spinazarin（2,3-二羟基-萘并或 2,3,5,8-四羟基-1,4-萘并醌）涉及用叠氮基取代氯原子，然后通过它们的酸性水解。该程序可用于天然生物活性菠菜素及其类似物的制备合成。
• Synthesis of water-soluble bisglutathionyl conjugates of 7-alkyl-5,6,8-trihydroxy-1,4-naphthoquinones
  作者：Yu. E. Sabutskii、S. G. Polonik

  DOI：10.1134/s1070428014050248

  日期：2014.5