(1,4-dihydroxynaphthalen-2-yl)(furan-2-yl)methanone | 1266253-44-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: (1,4-dihydroxynaphthalen-2-yl)(furan-2-yl)methanone
• 英文别名: 2-furoyl-1,4-naphthohydroquinone；2-(furan-2-yl)-1,4-dihydroxynapthohydroquinone；(1,4-Dihydroxynaphthalen-2-yl)-(furan-2-yl)methanone；(1,4-dihydroxynaphthalen-2-yl)-(furan-2-yl)methanone
• CAS: 1266253-44-4
• 化学式: C₁₅H₁₀O₄
• 分子量: 254.242
• InChiKey: KCKMWCFUCADDCU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1,4-dihydroxynaphthalen-2-yl)(furan-2-yl)methanone 在 magnesium sulfate 、 silver(l) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 13-hydroxy-13-(fur-2-yl)-7H-benzo[g]benzo[4,5]thiazolo[2,3-b]quinazoline-7,12-quinone
  参考文献：
  名称：

  2-酰基萘醌和2-氨基苯并噻唑之间的异环反应。抗增殖苯并[ g ]苯并噻唑并[2,3 - b ]喹唑啉-7,12-醌的合成新途径

  摘要：

  开发了一种方便的两步法，用于从2-酰基萘氢醌和2-氨基苯并噻唑制备苯并[ g ]苯并噻唑并[2,3 - b ]喹唑啉-7,12-醌。X射线晶体学支持杂环醌的结构。该方案为制备标题化合物提供了一种操作简单的策略，并显示出良好的功能灵活性和易于获得的起始原料。据报道，某些获得的杂环醌对前列腺，膀胱和乳腺人类来源的肿瘤细胞系具有显着的体外抗增殖活性。

  DOI：

  10.1016/j.tetlet.2015.07.034
• 作为产物：
  描述：

  糠醛 、 1,4-萘醌 以 苯 为溶剂， 生成 (1,4-dihydroxynaphthalen-2-yl)(furan-2-yl)methanone
  参考文献：
  名称：

  二羟基萘基芳基酮与微管蛋白秋水仙碱位点的结合抑制了微管组装。

  摘要：

  已经评估了二羟基萘基芳基酮1-5抑制微管组装和与微管蛋白结合的能力。化合物3、4和5显示出对秋水仙碱结合的竞争性抑制作用，对接分析表明它们与微管蛋白秋水仙碱结合口袋诱导片结合，而不是与微管结合。在所测定的化合物之间观察到的生物学活性的显着差异似乎与键合至羰基的芳基取代基的结构和位置有关。与碳环类似物5相比，含有杂环的化合物2、3和4对微管蛋白的亲和力更高。化合物4显示了该系列的最佳亲和力，IC50值为2.1μM，可抑制微管聚合和微管蛋白解离。常数为1.0±0.2μM，由热泳确定。尽管化合物4含有秋水仙碱中存在的三甲氧基苯基环，但它在体外破坏微管装配方面比化合物5更有效。与α-微管蛋白的Asn101的氢键似乎是化合物4彼此之间更高的亲和力的原因。

  DOI：

  10.1016/j.bbrc.2015.09.041

文献信息

• In Vitro Inhibition of Hsp90 Protein by Benzothiazoloquinazolinequinones Is Enhanced in The Presence of Ascorbate. A Preliminary In Vivo Antiproliferative Study
  作者：Jaime A. Valderrama、David Ríos、Giulio G. Muccioli、Pedro Buc Calderon、Julio Benites

  DOI：10.3390/molecules25040953

  日期：——

  A series of benzo[g]benzothiazolo[2,3-b]quinazoline-7,12-quinones were prepared from 2-acylnaphthohydroquinones and 2-aminobenzothiazoles and were evaluated for their in vitro antiproliferative activity. After screening using the MTT reduction assay, their IC50 values were calculated on a panel of cancer cells (T24, DU-145, MCF-7). Current standard anticancer drugs were included as control, and their calculated IC50 values were 7.8 and 23.5 µM for 5-fluorouracil and tamoxifen, respectively. Non-cancer cells (AG1523) were included to assess cancer cell sensitivity and drug selectivity. Four members of the series, with IC50 values from 0.11 to 2.98 µM, were chosen for further assays. The selected quinones were evaluated regarding their effects on cancer cell proliferation (clonogenic assay) and on Hsp90 and poly(ADPribose)polymerase (PARP) protein integrity. The most active compound (i.e., 15) substantially inhibited colony forming unit (CFU) formation at 0.25 µM. In the presence of ascorbate, it induced an oxidative cleavage of Hsp90 but had no effect on PARP protein integrity. In an in vivo animal model, it discreetly increased the mean survival time (m.s.t.) of tumor-bearing mice. In light of these results, compound 15 represents a potential lead-molecule to be further developed.

  一系列苯并[g]苯并噻唑[2,3-b]喹唑啉-7,12-醌类化合物是通过2-酰基萘羟喹醌和2-氨基苯并噻唑反应制备的，并对它们的体外抗增殖活性进行了评估。通过MTT还原实验筛选后，在一系列癌细胞（T24、DU-145、MCF-7）中计算了它们的IC50值。当前标准的抗癌药物被包括为对照，5-氟尿嘧啶和他莫昔芬的计算IC50值分别为7.8和23.5微米。非癌细胞（AG1523）被包括以评估癌细胞的敏感性和药物选择性。系列中的四个成员，其IC50值从0.11到2.98微米不等，被选定进行进一步的实验。选定的醌类化合物被评估其对癌细胞增殖（克隆形成实验）以及对Hsp90和聚(ADP核糖)聚合酶（PARP）蛋白完整性的影响。最活性的化合物（即15号）在0.25微米下显著抑制了克隆形成单位（CFU）的形成。在抗坏血酸存在的情况下，它诱导了Hsp90的氧化裂解，但对PARP蛋白的完整性没有影响。在体内动物模型中，它轻微增加了携带肿瘤的小鼠的平均存活时间（m.s.t.）。鉴于这些结果，化合物15代表了一个有潜力进一步开发的先导分子。
• Synthetic approaches and in vitro cytotoxic evaluation of 2-acyl-3-(3,4,5-trimethoxyanilino)-1,4-naphthoquinones
  作者：Jaime A. Valderrama、Mónica Cabrera、Julio Benites、David Ríos、Ricardo Inostroza-Rivera、Giulio G. Muccioli、Pedro Buc Calderon

  DOI：10.1039/c7ra03238b

  日期：——

  formation of the heterocyclic compounds is discussed in terms of the ring closure of C–C Michael type adduct intermediates through two alternative N–C-bond formations. The propensity of the substrates to undergo preferential C–C instead of C–N bond formation and the further heterocyclization of the C–C Michael type adduct intermediates is rationalized by using product stability parameters assessed by DFT

  2-酰基-1,4-萘醌与3,4,5-三甲氧基苯胺在有氧条件下反应，生成苯并菲啶醌，苯并咔唑和2-酰基-3-（3,4,5-三甲氧基苯胺基）-1,4-萘醌衍生品。关于杂环化合物的形成，将通过两个备选的N-C键形成对C–C Michael型加合物中间体的闭环进行讨论。通过使用DFT计算评估的产品稳定性参数，可以使底物发生优先C–C而不是C–N键形成的倾向以及C–C Michael型加合物中间体的进一步杂环化。初步结果报道了从2-酰基萘醌制备2-酰基-3-（3,4,5-三甲氧基苯胺基）-1,4-萘醌的便利方法及其对癌细胞的细胞毒活性。
• Discovery of New 2-Phenylamino-3-acyl-1,4-naphthoquinones as Inhibitors of Cancer Cells Proliferation: Searching for Intra-Cellular Targets Playing a Role in Cancer Cells Survival
  作者：Julio Benites、Jaime A. Valderrama、Álvaro Contreras、Cinthya Enríquez、Ricardo Pino-Rios、Osvaldo Yáñez、Pedro Buc Calderon

  DOI：10.3390/molecules28114323

  日期：——

  A series of 2-phenylamino-3-acyl-1,4-naphtoquinones were evaluated regarding their in vitro antiproliferative activities using DU-145, MCF-7 and T24 cancer cells. Such activities were discussed in terms of molecular descriptors such as half-wave potentials, hydrophobicity and molar refractivity. Compounds 4 and 11 displayed the highest antiproliferative activity against the three cancer cells and were therefore further investigated. The in silico prediction of drug likeness, using pkCSM and SwissADME explorer online, shows that compound 11 is a suitable lead molecule to be developed. Moreover, the expressions of key genes were studied in DU-145 cancer cells. They include genes involved in apoptosis (Bcl-2), tumor metabolism regulation (mTOR), redox homeostasis (GSR), cell cycle regulation (CDC25A), cell cycle progression (TP53), epigenetic (HDAC4), cell-cell communication (CCN2) and inflammatory pathways (TNF). Compound 11 displays an interesting profile because among these genes, mTOR was significantly less expressed as compared to control conditions. Molecular docking shows that compound 11 has good affinity with mTOR, unraveling a potential inhibitory effect on this protein. Due to the key role of mTOR on tumor metabolism, we suggest that impaired DU-145 cells proliferation by compound 11 is caused by a reduced mTOR expression (less mTOR protein) and inhibitory activity on mTOR protein.

  研究人员使用 DU-145、MCF-7 和 T24 癌细胞对一系列 2-苯基氨基-3-酰基-1,4-萘醌的体外抗增殖活性进行了评估。根据半波电位、疏水性和摩尔折射率等分子描述指标对这些活性进行了讨论。化合物 4 和 11 对三种癌细胞的抗增殖活性最高，因此被进一步研究。利用 pkCSM 和 SwissADME explorer 在线对药物相似性进行的硅学预测表明，化合物 11 是一个适合开发的先导分子。此外，还研究了 DU-145 癌细胞中关键基因的表达。这些基因包括参与凋亡（Bcl-2）、肿瘤代谢调节（mTOR）、氧化还原平衡（GSR）、细胞周期调节（CDC25A）、细胞周期进展（TP53）、表观遗传（HDAC4）、细胞-细胞通讯（CCN2）和炎症通路（TNF）的基因。化合物 11 显示出有趣的特征，因为在这些基因中，与对照条件相比，mTOR 的表达明显减少。分子对接显示，化合物 11 与 mTOR 具有良好的亲和力，揭示了对该蛋白的潜在抑制作用。鉴于 mTOR 在肿瘤代谢中的关键作用，我们认为化合物 11 对 DU-145 细胞增殖的抑制作用是由 mTOR 表达减少（mTOR 蛋白减少）和对 mTOR 蛋白的抑制活性引起的。
• The solar-chemical photo-Friedel–Crafts heteroacylation of 1,4-quinones
  作者：Julio Benites、David Rios、Pilar Díaz、Jaime A. Valderrama

  DOI：10.1016/j.tetlet.2010.11.149

  日期：2011.2

  Photochemical reactions between 1,4-benzo- and 1,4-naphthoquinone and several heteroaromatic carbaldehydes were investigated under solar irradiation conditions. These reactions gave the corresponding heteroacylated hydroquinones in the range 71%-92% yield. (C) 2010 Elsevier Ltd. All rights reserved.
• GREEN SYNTHETIC APPROACHES TO FUROYLNAPHTHOHYDROQUINONE AND JUGLONE
  作者：BENITES JULIO、CORTES MICHAEL、MIRANDA LUIS、ESTELA CYNTHIA、RIOS DAVID、ARENAS JORGE、VALDERRAMA JAIME A.

  DOI：10.4067/s0717-97072014000200012

  日期：——