4-hydroxy-3-methoxyxanthone | 39731-27-6

• 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: 4-hydroxy-3-methoxyxanthone
• 英文别名: 4-hydroxy-3-methoxy-9H-xanthen-9-one；4-hydroxy-3-methoxyxanthen-9-one
• CAS: 39731-27-6
• 化学式: C₁₄H₁₀O₄
• 分子量: 242.231
• InChiKey: AATWPLNNZKLWEK-UHFFFAOYSA-N

物化性质

• 沸点：
  425.8±45.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-hydroxy-3-methoxyxanthone 在 乌洛托品 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 54.0h， 生成 1-(hydroxymethyl)-3,4-dimethoxy-9H-xanthen-9-one
  参考文献：
  名称：

  新型胺化氧杂蒽酮作为潜在 p53 活化剂的合成、生物学评价和计算机研究

  摘要：

  呫吨酮支架已被视为一种有吸引力的化学工具，用于寻找具有抗肿瘤活性的生物活性分子，特别是两种呫吨酮衍生物，12-羟基-2,2-二甲基-3,4-二氢-2H,6H-吡喃 [3] ,2-b]xanthen-6-one (4) 和 3,4-dimethoxy-9-oxo-9H-xanthene-1-carbaldehyde (5)，被描述为鼠双分钟 2 (MDM2)-p53 抑制剂和分别是 TAp73 激活剂。呫吨酮 5 被用作构建带有所述 MDM2-p53 抑制剂化学部分的 3,4-双氧合呫吨酮文库的起点。成功合成了 11 种胺化氧杂蒽酮，并使用基于酵母细胞的测定对其破坏 MDM2-p53 相互作用的能力进行了初步筛选。通过这种方法，通过抑制与 MDM2 的相互作用，氧杂蒽酮 37 被鉴定为推定的 p53 激活剂。Xanthone 37 以 p53 依赖性方式抑制人结肠腺癌 HCT116 细胞系的生长。氧杂蒽酮

  DOI：

  10.3390/molecules24101975
• 作为产物：
  描述：

  1,2,3-三甲氧基苯 在 哌啶 、 aluminum (III) chloride 作用下， 以 乙醚 、 水 为溶剂， 反应 53.0h， 生成 4-hydroxy-3-methoxyxanthone
  参考文献：
  名称：

  新型胺化氧杂蒽酮作为潜在 p53 活化剂的合成、生物学评价和计算机研究

  摘要：

  呫吨酮支架已被视为一种有吸引力的化学工具，用于寻找具有抗肿瘤活性的生物活性分子，特别是两种呫吨酮衍生物，12-羟基-2,2-二甲基-3,4-二氢-2H,6H-吡喃 [3] ,2-b]xanthen-6-one (4) 和 3,4-dimethoxy-9-oxo-9H-xanthene-1-carbaldehyde (5)，被描述为鼠双分钟 2 (MDM2)-p53 抑制剂和分别是 TAp73 激活剂。呫吨酮 5 被用作构建带有所述 MDM2-p53 抑制剂化学部分的 3,4-双氧合呫吨酮文库的起点。成功合成了 11 种胺化氧杂蒽酮，并使用基于酵母细胞的测定对其破坏 MDM2-p53 相互作用的能力进行了初步筛选。通过这种方法，通过抑制与 MDM2 的相互作用，氧杂蒽酮 37 被鉴定为推定的 p53 激活剂。Xanthone 37 以 p53 依赖性方式抑制人结肠腺癌 HCT116 细胞系的生长。氧杂蒽酮

  DOI：

  10.3390/molecules24101975

文献信息

• 1H and13C NMR Spectroscopy of mono-, di-, tri- and tetrasubstituted xanthones
  作者：Eduarda G. R. Fernandes、Artur M. S. Silva、José A. S. Cavaleiro、Francisco M. Silva、M. Fernanda、M. Borges、Madalena M. M. Pinto

  DOI：10.1002/(sici)1097-458x(199804)36:4<305::aid-omr193>3.0.co;2-n

  日期：1998.4

  The structural elucidation of 24 xanthones with different substitution patterns was performed by spectroscopic methods, namely 2D NMR techniques, such as correlation spectroscopy (COSY), nuclear Overhauser effect (NOE), heteronuclear correlation (HETCOR) and a 1D NMR technique, selective insensitive nuclei enhanced by polarization transfer (INEPT). © 1997 John Wiley & Sons, Ltd.

  24种不同取代模式的氧杂蒽酮的结构解析是通过光谱方法进行的，即二维核磁共振技术，如相关光谱（COSY）、核奥弗豪泽效应（NOE）、异核相关（HETCOR）和一维核磁共振技术、选择性不敏感核通过极化转移 (INEPT) 增强。© 1997 约翰威利父子公司。
• Newly Synthesized Oxygenated Xanthones as Potential P-Glycoprotein Activators: In Vitro, Ex Vivo, and In Silico Studies
  作者：Eva Martins、Vera Silva、Agostinho Lemos、Andreia Palmeira、Ploenthip Puthongking、Emília Sousa、Carolina Rocha-Pereira、Carolina Ghanem、Helena Carmo、Fernando Remião、Renata Silva

  DOI：10.3390/molecules24040707

  日期：——

  P-glycoprotein (P-gp) plays a crucial role in the protection of susceptible organs, by significantly decreasing the absorption/distribution of harmful xenobiotics and, consequently, their toxicity. Therefore, P-gp has been proposed as a potential antidotal pathway, when activated and/or induced. Knowing that xanthones are known to interact with P-gp, the main goal was to study P-gp induction or/and activation by six new oxygenated xanthones (OX 1-6). Furthermore, the potential protection of Caco-2 cells against paraquat cytotoxicity was also assessed. The most promising compound was further tested for its ability to increase P-gp activity ex vivo, using everted intestinal sacs from adult Wistar-Han rats. The oxygenated xanthones interacted with P-gp in vitro, increasing P-gp expression and/or activity 24 h after exposure. Additionally, after a short-incubation period, several xanthones were identified as P-gp activators, as they immediately increased P-gp activity. Moreover, some xanthones decreased PQ cytotoxicity towards Caco-2 cells, an effect prevented under P-gp inhibition. Ex vivo, a significant increase in P-gp activity was observed in the presence of OX6, which was selectively blocked by a model P-gp inhibitor, zosuquidar, confirming the in vitro results. Docking simulations between a validated P-gp model and the tested xanthones predicted these interactions, and these compounds also fitted onto previously described P-gp induction and activation pharmacophores. In conclusion, the in vitro, ex vivo, and in silico results suggest the potential of some of the oxygenated xanthones in the modulation of P-gp, disclosing new perspectives in the therapeutics of intoxications by P-gp substrates.

  P-糖蛋白（P-gp）在保护易受损害器官方面发挥着关键作用，通过显著降低有害异物的吸收/分布，从而降低其毒性。因此，当P-gp被激活和/或诱导时，已被提议作为潜在的解毒途径。鉴于黄酮类化合物已知与P-gp相互作用，主要目标是研究六种新的含氧黄酮类化合物（OX 1-6）对P-gp的诱导和/或激活。此外，还评估了Caco-2细胞对百草枯细胞毒性的潜在保护作用。最有前途的化合物进一步被测试其在体外增加P-gp活性的能力，使用成年Wistar-Han大鼠的转出肠囊。这些含氧黄酮类化合物在体外与P-gp相互作用，增加P-gp表达和/或活性，在暴露后24小时。此外，在短时间培养后，几种黄酮类化合物被确定为P-gp激活剂，因为它们立即增加了P-gp活性。此外，一些黄酮类化合物减少了对Caco-2细胞的百草枯细胞毒性，这种效应在P-gp抑制下被阻止。在体外实验中，存在OX6时P-gp活性显著增加，这种增加被一种模型P-gp抑制剂zosuquidar选择性地阻断，从而证实了体外实验结果。通过验证的P-gp模型和被测试的黄酮类化合物之间的对接模拟预测了这些相互作用，这些化合物也符合先前描述的P-gp诱导和激活药效团。总之，体外、体内和计算机模拟结果表明，一些含氧黄酮类化合物在调节P-gp方面具有潜力，揭示了P-gp底物中毒治疗中的新视角。
• Enantioselectivity of Chiral Derivatives of Xanthones in Virulence Effects of Resistant Bacteria
  作者：Fernando Durães、Sara Cravo、Joana Freitas-Silva、Nikoletta Szemerédi、Paulo Martins-da-Costa、Eugénia Pinto、Maria Elizabeth Tiritan、Gabriella Spengler、Carla Fernandes、Emília Sousa、Madalena Pinto

  DOI：10.3390/ph14111141

  日期：——

  Antimicrobial peptides are one of the lines of defense produced by several hosts in response to bacterial infections. Inspired by them and recent discoveries of xanthones as bacterial efflux pump inhibitors, chiral amides with a xanthone scaffold were planned to be potential antimicrobial adjuvants. The chiral derivatives of xanthones were obtained by peptide coupling reactions between suitable xanthones with enantiomerically pure building blocks, yielding derivatives with high enantiomeric purity. Among 18 compounds investigated for their antimicrobial activity against reference strains of bacteria and fungi, antibacterial activity for the tested strains was not found. Selected compounds were also evaluated for their potential to inhibit bacterial efflux pumps. Compound (R,R)-8 inhibited efflux pumps in the Gram-positive model tested and three compounds, (S,S)-8, (R)-17 and (R,S)-18, displayed the same activity in the Gram-negative strain used. Studies were performed on the inhibition of biofilm formation and quorum-sensing, to which the enantiomeric pair 8 displayed activity for the latter. To gain a better understanding of how the active compounds bind to the efflux pumps, docking studies were performed. Hit compounds were proposed for each activity, and it was shown that enantioselectivity was noticeable and must be considered, as enantiomers displayed differences in activity.

  抗菌肽是一种由多种宿主产生的防御线之一，用于应对细菌感染。受到它们的启发以及最近发现的黄酮类化合物作为细菌外排泵抑制剂，我们计划设计具有黄酮骨架的手性酰胺作为潜在的抗菌辅助剂。通过适当的黄酮与对映异构纯的构建块进行肽偶联反应，获得了黄酮的手性衍生物，产物的对映纯度较高。在对18种化合物进行抗菌活性研究时，针对细菌和真菌的参考菌株，未发现对测试菌株的抗菌活性。还评估了选择性化合物对抑制细菌外排泵的潜力。化合物(R,R)-8抑制了测试的革兰氏阳性模型中的外排泵，而三种化合物(S,S)-8、(R)-17和(R,S)-18在使用的革兰氏阴性菌株中显示了相同的活性。对生物膜形成和群体感应的抑制研究表明，对映异构体8对后者显示了活性。为了更好地了解活性化合物如何与外排泵结合，进行了对接研究。对于每种活性提出了命中化合物，并且显示出对映选择性是显著的，必须予以考虑，因为对映异构体在活性上显示出差异。
• Pyranoxanthones: Synthesis, growth inhibitory activity on human tumor cell lines and determination of their lipophilicity in two membrane models
  作者：Carlos M.G. Azevedo、Carlos M.M. Afonso、José X. Soares、Salette Reis、Diana Sousa、Raquel T. Lima、M. Helena Vasconcelos、Madalena Pedro、João Barbosa、Luís Gales、Madalena M.M. Pinto

  DOI：10.1016/j.ejmech.2013.09.012

  日期：2013.11

  The benzopyran and dihydrobenzopyran moieties can be considered as "privileged motifs" in drug discovery being good platforms for the search of new bioactive compounds. These moieties are commonly found fused to the xanthonic scaffold belonging to the biologically important family of the generally designated prenylated xanthones. Several pyranoxanthones have shown promising antitumor activity and since most of them are from natural origin, the biosynthetic pathway only allows a particular pattern of substitution which limits their structural diversity and renders any broad structure activity study hard to be established. Accordingly, with the aim of rationalizing the importance of the fused ring orientation and oxygenation pattern in pyranoxanthones, this study describes the synthesis of 14 new pyranoxanthones and evaluation of their cell growth inhibitory activity in four human tumor cell lines as well as their lipophilicity in two membrane models. This systematic approach allowed establishing structure activity and structure lipophilicity relationships for the obtained compounds in combination with 6 previously described compounds. From this work an angular pyranoxanthone scaffold emerged as particularly promising, presenting a potent cell growth inhibitory activity and suitable drug-like lipophilicity. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis, Biological Evaluation, and In Silico Studies of Novel Aminated Xanthones as Potential p53-Activating Agents
  作者：Agostinho Lemos、Ana Sara Gomes、Joana B. Loureiro、Pedro Brandão、Andreia Palmeira、Madalena M. M. Pinto、Lucília Saraiva、Maria Emília Sousa

  DOI：10.3390/molecules24101975

  日期：——

  p53-activating agent through inhibition of interaction with MDM2. Xanthone 37 inhibited the growth of human colon adenocarcinoma HCT116 cell lines in a p53-dependent manner. The growth inhibitory effect of xanthone 37 was associated with the induction of G1-phase cell cycle arrest and increased protein expression levels of p53 transcriptional targets. These results demonstrated the potential usefulness

  呫吨酮支架已被视为一种有吸引力的化学工具，用于寻找具有抗肿瘤活性的生物活性分子，特别是两种呫吨酮衍生物，12-羟基-2,2-二甲基-3,4-二氢-2H,6H-吡喃 [3] ,2-b]xanthen-6-one (4) 和 3,4-dimethoxy-9-oxo-9H-xanthene-1-carbaldehyde (5)，被描述为鼠双分钟 2 (MDM2)-p53 抑制剂和分别是 TAp73 激活剂。呫吨酮 5 被用作构建带有所述 MDM2-p53 抑制剂化学部分的 3,4-双氧合呫吨酮文库的起点。成功合成了 11 种胺化氧杂蒽酮，并使用基于酵母细胞的测定对其破坏 MDM2-p53 相互作用的能力进行了初步筛选。通过这种方法，通过抑制与 MDM2 的相互作用，氧杂蒽酮 37 被鉴定为推定的 p53 激活剂。Xanthone 37 以 p53 依赖性方式抑制人结肠腺癌 HCT116 细胞系的生长。氧杂蒽酮