4-[2-(4-羟基-3-甲氧苯基)乙基]-2,6-二甲氧基-苯酚 | 108853-14-1

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 4-[2-(4-羟基-3-甲氧苯基)乙基]-2,6-二甲氧基-苯酚
• 中文别名: 石槲酚；石斛酚；石斜氛
• 英文名称: moscatilin
• 英文别名: 1-(4-hydroxy-3-methoxyphenyl)-2-(4-hydroxy-3,5-dimethoxyphenyl)ethane；(4-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2,6-dimethoxyphenol)；4-(2-(4-hydroxy-3-methoxyphenyl)ethyl)-2,6-dimethoxyphenol；4-[2-(4-hydroxy-3-methoxyphenyl)ethyl]-2,6-dimethoxyphenol；4,4′-dihydroxyl-3,3′,5-trimethoxybibenzyl；4,4′-dihydroxy-3,3′,5-trimethoxybibenzyl；Dendrophenol
• CAS: 108853-14-1
• 化学式: C₁₇H₂₀O₅
• 分子量: 304.343
• InChiKey: YTRAYUIKLRABOQ-UHFFFAOYSA-N

物化性质

• 熔点：
  87-89℃ (ethyl ether )
• 沸点：
  454.1±40.0 °C
• 密度：
  1.208±0.06 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  溶于二甲基亚砜
• 保留指数：
  2569.2

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  68.2
• 氢给体数：
  2
• 氢受体数：
  5

制备方法与用途

生物活性

Dendrophenol 是从 Dendrobium loddigesii Rolfe 的茎中分离得到的，用作 NF-κB 抑制剂，并具有抗肿瘤活性。

靶点

• NF-κB

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 4-[2-(4-羟基-3-甲氧苯基)乙基]-2,6-二甲氧基-苯酚 以 甲醇 、 乙醚 为溶剂， 以0.015 g的产率得到5-[2-(3,4-二甲氧苯基)乙基]-1,2,3-三甲氧基苯
  参考文献：
  名称：

  Majumder; Bandyopadhyay, Saswati, Journal of the Indian Chemical Society, 2010, vol. 87, # 2, p. 221 - 234

  摘要：

  DOI：
• 作为产物：
  描述：

  4-羟基-3-甲氧基苄醇 在 吡啶 、 18-冠醚-6 、 palladium 10% on activated carbon 、 氢气 、 sodium methylate 、 三溴化磷 、 potassium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 33.0h， 生成 4-[2-(4-羟基-3-甲氧苯基)乙基]-2,6-二甲氧基-苯酚
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Gigantol Derivatives as Potential Agents in Prevention of Diabetic Cataract

  摘要：

  作为我们致力于开发天然抗糖尿病性白内障药物的延续，从石斛中分离出巨花素，并发现它能抑制醛糖还原酶（AR）和诱导型一氧化氮合酶（iNOS）的活性，这两种酶在糖尿病性白内障的发展和进展中起着重要作用。为了提高其生物效力和便于作为治疗剂使用，设计并合成了巨花素（化合物14f）及一系列新衍生物。这些衍生物在苯环上有不同的取代基（化合物4、5、8、14a-e），用具有更大立体障碍的环替代苯环（化合物10、17c），或修改碳链（化合物17a、17b、21、23、25）。所有衍生物在体外对AR和iNOS的活性以及在D-半乳糖诱导的人晶状体上皮细胞凋亡中的作用进行了测试。化合物5、10、14a、14b、14d、14e、14f、17b、17c、23和25抑制了AR的活性，IC50值范围为5.02至288.8 μM。化合物5、10、14b和14f抑制了iNOS的活性，IC50范围为432.6至1188.7 μM。化合物5、8、10、14b、14f和17c保护细胞免受D-半乳糖诱导的凋亡，存活率范围为55.2至76.26%。在巨花素及其衍生物中，化合物10显示出最大的生物效力，值得开发为糖尿病性白内障的治疗剂。

  DOI：

  10.1371/journal.pone.0141092

文献信息

• Dihydrostilbenes and diarylpropanes: Synthesis and in vitro pharmacological evaluation as potent nitric oxide production inhibition agents
  作者：Ha Young Jang、Hyeong Jin Park、Kongara Damodar、Jin-Kyung Kim、Jong-Gab Jun

  DOI：10.1016/j.bmcl.2016.10.034

  日期：2016.11

  An efficient synthesis of dihydrostilbenes (1-5) and diarylpropanes (6-10) is achieved from the commercially available starting materials and Wittig-Horner reaction, Claisen-Schmidt condensation and hydrogenation as key steps. Later, their nitric oxide (NO) production inhibition effects were evaluated in lipopolysaccharide (LPS)-induced RAW-264.7 macrophages as an indicator of anti-inflammatory activity

  由市售的起始原料和Wittig-Horner反应，Claisen-Schmidt缩合和氢化作为关键步骤，可以有效地合成二氢苯乙烯（1-5）和二芳基丙烷（6-10）。随后，在脂多糖（LPS）诱导的RAW-264.7巨噬细胞中评估了它们对一氧化氮（NO）产生的抑制作用，作为抗炎活性的指标。除化合物2、6和8外，所有受试化合物均以浓度依赖性方式显着降低NO的产生，除化合物1外，未显示出明显的细胞毒性。两种化合物，即化合物9（辛二丙烷B）（100％； IC50 =1.84μM）具有最强的NO抑制活性，甚至比阳性对照L-NMMA（90.1％； IC50 =2.73μM）更强，其次是化合物4（75.5％； IC50 = 2）。浓度为10μM（98μM），并且该发现还与LPS刺激的诱导型一氧化氮合酶表达的抑制有关。我们的研究表明，化合物9，具有3“，4”-二甲氧基苯基和3'，4'-二羟基-2'-甲氧基苯基基序的1
• 다이하이드로스틸벤 합성방법 및 이를 포함하는 항염증 약학 조성물
  申请人：Industry Academic Cooperation Foundation, Hallym University 한림대학교 산학협력단(220070195175) BRN ▼221-82-10284

  公开号：KR20180016809A

  公开（公告）日：2018-02-20

  과제: 부작용 없는 효과적인 항염증제를 제공하려는 것. 해결수단: 본 발명자들은 개시물질로부터 다이하이드로스틸벤 및 그 유도체들 (화합물 1 내지 5)을 높은 수율로 효과적으로 합성하는 방법을 발명하였다. 또한, 그들의 항염증 효과를 LPS-유도 RAW-264.7 대식세포에서 평가하였다. 다이하이드로스틸벤의 화합물은 세포독성을 나타내지 않으며, 10μM 농도에서 LPS로 유도되는 산화질소 생성을 약하게 또는 잘 저해하는 것으로 나타났다.

  任务：提供无副作用的有效抗炎药。解决方案：本发明人发明了一种从起始物质中高产率地有效合成二氢苯并及其衍生物（化合物1至5）的方法。此外，他们评估了这些化合物在LPS诱导的RAW-264.7巨噬细胞中的抗炎作用。二氢苯并化合物表现出不细胞毒性，并且在10μM浓度下显示对LPS诱导的氧化亚氮生成的轻微或有效抑制。
• Structural modification of resveratrol analogue exhibits anticancer activity against lung cancer stem cells via suppression of Akt signaling pathway
  作者：Sunisa Thongsom、Satapat Racha、Korrakod Petsri、Zin Zin Ei、Kittichate Visuttijai、Sohsuke Moriue、Masashi Yokoya、Pithi Chanvorachote

  DOI：10.1186/s12906-023-04016-6

  日期：——

  Compound with cancer stem cell (CSC)-suppressing activity is promising for the improvement of lung cancer clinical outcomes. Toward this goal, we discovered the CSC-targeting activity of resveratrol (RES) analog moscatilin (MOS). With slight structural modification from RES, MOS shows dominant cytotoxicity and CSC-suppressive effect.

  Three human lung cancer cell lines, namely H23, H292, and A549, were used to compare the effects of RES and MOS. Cell viability and apoptosis were determined by the MTT assay and Hoechst33342/PI double staining. Anti-proliferative activity was determined by colony formation assay and cell cycle analysis. Intracellular reactive oxygen species (ROS) were measured by fluorescence microscopy using DCFH₂-DA staining. CSC-rich populations of A549 cells were generated, and CSC markers, and Akt signaling were determined by Western blot analysis and immunofluorescence. Molecular docking and molecular dynamics (MD) simulations were used to predict the possible binding of the compound to Akt protein.

  In this study, we evaluated the effects of RES and MOS on lung cancer and its anti-CSC potential. Compared with RES, its analog MOS more effectively inhibited cell viability, colony formation, and induced apoptosis in all lung cancer cell lines (H23, H292, and A549). We further investigated the anti-CSC effects on A549 CSC-rich populations and cancer adherent cells (A549 and H23). MOS possesses the ability to suppress CSC-like phenotype of lung cancer cells more potent than RES. Both MOS and RES repressed lung CSCs by inhibiting the viability, proliferation, and lung CSC-related marker CD133. However, only MOS inhibits the CSC marker CD133 in both CSC-rich population and adherent cells. Mechanistically, MOS exerted its anti-CSC effects by inhibiting Akt and consequently restored the activation of glycogen synthase kinase 3β (GSK-3β) and decreased the pluripotent transcription factors (Sox2 and c-Myc). Thus, MOS inhibits CSC-like properties through the repression of the Akt/GSK-3β/c-Myc pathway. Moreover, the superior inhibitory effects of MOS compared to RES were associated with the improved activation of various mechanism, such as cell cycle arrest at G2/M phase, production of ROS-mediated apoptosis, and inhibition of Akt activation. Notably, the computational analysis confirmed the strong interaction between MOS and Akt protein. MD simulations revealed that the binding between MOS and Akt1 was more stable than RES, with MM/GBSA binding free energy of − 32.8245 kcal/mol at its allosteric site. In addition, MOS interacts with Trp80 and Tyr272, which was a key residue in allosteric inhibitor binding and can potentially alter Akt activity.

  Knowledge about the effect of MOS as a CSC-targeting compound and its interaction with Akt is important for the development of drugs for the treatment of CSC-driven cancer including lung cancer.

  摘要 研究背景 具有抑制癌症干细胞（CSC）活性的化合物有望改善肺癌的临床预后。为此，我们发现了白藜芦醇（RES）类似物莫斯卡替林（MOS）的癌干细胞靶向活性。与白藜芦醇相比，MOS在结构上略有改动，但却显示出显著的细胞毒性和CSC抑制作用。 研究方法 采用三种人类肺癌细胞系，即 H23、H292 和 A549，比较 RES 和 MOS 的作用。细胞活力和凋亡通过 MTT 试验和 Hoechst33342/PI 双染法进行测定。抗增殖活性通过集落形成试验和细胞周期分析来确定。细胞内活性氧（ROS）通过 DCFH2-DA 染色荧光显微镜测定。生成富含 CSC 的 A549 细胞群，并通过 Western 印迹分析和免疫荧光测定 CSC 标记和 Akt 信号转导。分子对接和分子动力学（MD）模拟用于预测化合物与 Akt 蛋白的可能结合。 研究结果 本研究评估了 RES 和 MOS 对肺癌的影响及其抗 CSC 的潜力。与 RES 相比，其类似物 MOS 能更有效地抑制所有肺癌细胞系（H23、H292 和 A549）的细胞活力、集落形成并诱导细胞凋亡。我们进一步研究了 MOS 对 A549 CSC 富集群体和癌粘附细胞（A549 和 H23）的抗 CSC 作用。与 RES 相比，MOS 具有更强的抑制肺癌细胞 CSC 样表型的能力。MOS和RES都能抑制肺CSC的活力、增殖和肺CSC相关标记物CD133。但是，只有 MOS 能抑制富含 CSC 群体和粘附细胞中的 CSC 标记 CD133。从机理上讲，MOS通过抑制Akt发挥抗CSC作用，从而恢复糖原合酶激酶3β（GSK-3β）的活化并减少多能转录因子（Sox2和c-Myc）。因此，MOS通过抑制Akt/GSK-3β/c-Myc通路来抑制CSC样特性。此外，MOS的抑制作用优于RES，这与MOS激活了细胞周期停滞在G2/M期、产生ROS介导的细胞凋亡和抑制Akt活化等多种机制有关。值得注意的是，计算分析证实了 MOS 与 Akt 蛋白之间的强相互作用。MD 模拟显示，MOS 与 Akt1 的结合比 RES 更稳定，其异构位点的 MM/GBSA 结合自由能为 - 32.8245 kcal/mol。此外，MOS 还与 Trp80 和 Tyr272 相互作用，而 Trp80 和 Tyr272 是异构抑制剂结合的关键残基，有可能改变 Akt 的活性。 结论 了解 MOS 作为一种 CSC 靶向化合物的作用及其与 Akt 的相互作用对于开发治疗 CSC 驱动的癌症（包括肺癌）的药物非常重要。
• Method of using dihydro-resveratrol or its stilbenoid derivatives and/or chemical variants in treatment of tumorous pathologies
  申请人：Hong Kong Baptist University

  公开号：US10017442B2

  公开（公告）日：2018-07-10

  The present invention relates to a polyphenol derivative of the stilbenoid family, namely trans-3,5,4′-trihydroxybibenzyl, also known as dihydro-resveratrol, as a remedial agent. In particular, the present invention presents the usage of dihydro-resveratrol or its derivatives/chemical variants in the manufacture of a medicament for the treatment of tumors or cancers. The dihydrostilbenes can be used in the treatment or delay of progression of a cancer in a patient or used in a pharmaceutical formulation for the aforementioned purposes.

  本发明涉及一种白藜芦醇家族的多酚衍生物，即反式-3,5,4′-三羟基白藜芦醇，又称二氢白藜芦醇，可作为一种治疗剂。特别是，本发明提出了二氢白藜芦醇或其衍生物/化学变体在制造治疗肿瘤或癌症的药物中的用途。二氢白藜芦醇可用于治疗或延缓患者的癌症进展，或用于上述目的的药物制剂中。
• Skin-protection composition containing Dendrobium-based ingredients
  申请人：Hong Kong Baptist University

  公开号：US10188590B2

  公开（公告）日：2019-01-29

  The present invention relates to a skin-protection composition that comprises stilbenoid(s) and/or stilbenoid-containing extract(s) obtained from Dendrobium plants, such as Dendrobium officinale and Dendrobium nobile for the management of melanogenesis, skin-darkening and skin-aging. More particularly, it relates to the usage of Dendrobium ingredients and stilbenoids to reduce the formation of melanin in melanocytes. It also relates to the usage of Dendrobium ingredients and stilbenoids to reduce the generation of reactive oxygen species and oxidative free radicals. This invention relates to the use Dendrobium-derived extracts or ingredients or stilbenoids in the formulation of skin-protection, skin-whitening and/or anti-skin aging products.

  本发明涉及一种皮肤保护组合物，该组合物包含从铁皮石斛植物（如Dendrobium officinale和Dendrobium nobile）中提取的类石斛素和/或含类石斛素的提取物，用于控制黑色素生成、皮肤变黑和皮肤老化。更具体地说，它涉及使用石斛成分和石斛素来减少黑色素细胞中黑色素的形成。本发明还涉及使用铁皮石斛成分和类石斛烯减少活性氧和氧化自由基的生成。本发明涉及在皮肤保护、皮肤美白和/或抗衰老产品配方中使用铁皮石斛提取物或成分或类石斛素。