oxysophocarpine | 26904-64-3

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: oxysophocarpine
• 英文别名: Matridin-15-one, 13,14-didehydro-, 1-oxide；(1R,2R,9S,13R,17S)-13-oxido-7-aza-13-azoniatetracyclo[7.7.1.02,7.013,17]heptadec-4-en-6-one
• CAS: 26904-64-3
• 化学式: C₁₅H₂₂N₂O₂
• 分子量: 262.352
• InChiKey: QMGGMESMCJCABO-JARXUMMXSA-N

物化性质

• 熔点：
  73-76 °C
• 溶解度：
  溶于氯仿和水

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  38.4
• 氢给体数：
  0
• 氢受体数：
  2

制备方法与用途

氧化槐果碱简介

氧化槐果碱是从豆根槐属植物苦参（Sophora flavescens Ait）或豆科植物苦豆子（Sophora subprostrata chrnet T.Chen）中分离出来的生物碱，是中草药的主要有效成分。它是一种白色或类白色结晶性粉末，无臭、味苦。

氧化槐果碱具有多种作用，如升高白细胞数、加强机体免疫力，并对抗痢疾杆菌、皮肤真菌、阿米巴原虫和滴虫等感染有抑制作用；还具有利尿、平喘、催眠、抗心律失常等多种功效。内服可用于治疗急性菌痢、扁桃体炎、乳腺炎、盆腔炎、淋巴结炎、支气管炎、喘息、心律失常、白细胞低下等症状，同时对牛皮癣和失眠也有一定的疗效。

制备方法

一种从狼牙刺花中提取氧化槐果碱的方法包括以下步骤：

1. 预处理：称取香菇，按照料液比1g:30mL加入水中，在40-50℃加热40-60分钟，冷却后过滤。回收利用香菇；将狼牙刺花和得到的香菇滤液按料液比1:8混合，在3-6℃下浸泡2小时，每隔20分钟翻动搅拌一次，过滤后得到预处理过的狼牙刺花。

2. 提取：取步骤（1）中预处理过的狼牙刺花，按照料液比1g:8mL加入至少含有一种有机溶剂的溶液，浸泡72小时。过滤后收集滤液和滤渣，滤渣按上述比例继续浸泡48小时，再过滤收集滤液。合并两次得到的滤液，并通过旋转蒸发仪减压浓缩得到氧化槐果碱粗提物浸膏。

3. 提取：将步骤（1）中预处理过的狼牙刺花按照料液比1g:8mL加入至少含有一种有机溶剂的溶液，浸泡72小时。过滤后收集滤液和滤渣，滤渣按上述比例继续浸泡48小时，再过滤收集滤液，并通过真空浓缩得到氧化槐果碱粗提物浸膏。

将步骤（2）中两次得到的氧化槐果碱粗提物浸膏合并备用。

3. 水沉除杂：向步骤（2）最终得到的氧化槐果碱粗提物浸膏中加入3-5倍质量的水，用氨水调节pH至11，室温下静置48小时后过滤，收集滤液。

4. 纯化分离：将步骤（3）中的滤液经过真空浓缩得到浓缩膏、浓缩膏真空干燥后采用甲醇和二氯甲烷为洗脱液进行硅胶柱分离。加入乙醚进行结晶分离，再用丙酮重结晶后进行干燥，即得到氧化槐果碱纯品。

生物活性

Oxysophocarpine 对中枢神经系统和周围神经系统具有神经保护作用及抗伤害感受性。此外，它还抑制口腔鳞状细胞癌（OSCC）的生长与转移。

体外研究

• Oxysophocarpine (5 μM) 可以在体外抑制 SCC-9 和 SCC-15 口腔鳞状细胞癌（OSCC）细胞的增殖并减少其迁移和侵袭能力。

化学性质

Oxysophocarpine 水、甲醇、乙醇、氯仿、苯中难溶，易溶于丙酮。

用途

• 用于含量测定/鉴定/药理实验等。
• 药理药效：升高白细胞数，加强机体免疫力，并对抗痢疾杆菌、皮肤真菌、阿米巴原虫和滴虫感染。还具有利尿、平喘、催眠及抗心律失常等多种作用。

反应信息

• 作为反应物：
  描述：

  oxysophocarpine 在 sodium hydroxide 作用下， 以 水 为溶剂， 反应 10.0h， 以45.2%的产率得到
  参考文献：
  名称：

  Identification of UQCRB as an oxymatrine recognizing protein using a T7 phage display screen

  摘要：

  Ethnopharmacological relevance: Sophora flavescens Aiton (Radix Sophorae Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic hepatitis B (CHB), and has the ability to clear heat and dampness from the body. Oxymatrine is one of the major bioactive compounds extracted from Sophora flavescens Aiton and constitutes more than 90% of the oxymatrine injection commonly used for CHB treatment in clinics in China.Aim of the study: We aim to analyze the protein binding target of oxymatrine in treating CHB by screening a T7 phage display cDNA library of human CHB and examine the biochemistry of protein-ligand binding between oxymatrine and its ligands.Materials and methods: A T7 phage cDNA library of human CHB was biopanned by affinity selection using oxymatrine as bait. The interaction of oxymatrine with its candidate binding protein was investigated by affinity assay, molecular docking, Isothermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR).Results: A library of potential oxymatrine binding peptides was generated. Ubiquinol-cytochrome c reductase binding protein (UQCRB) was one of the candidate binding proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the oxymatrine group were significantly higher than that in the control group, biotin group, and matrine group (p < 0.05 or p < 0.01). Three-dimensional structure modeling of the UQCRB with oxymatrine showed that their binding interfaces matched and oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and G1u91. The binding affinity constant (Kb) from SPR was 4.2 mM. The Kb from ITC experiment was 3.9 mM and stoichiometry was fixed as 1, which fit very well with the result of SPR The binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as hydrogen bonds and polar interactions as the heat released was about 157 kcal/mol and Delta G was less than zero.Conclusions: In this study, using the 17 phage display system, we have identified UQCRB as a direct binding protein of oxymatrine. Furthermore, the specificity and molecular interaction of oxymatrine with UQCRB were also determined. The binding of UQCRB to oxymatrine suggests that UQCRB is a potential target of oxymatrine in treating CHB. These results provide new understanding into the mechanism of oxymatrine and insights into the strategy on the treatment of CHB. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.jep.2016.08.007
• 作为产物：
  描述：

  布雷菲德菌素A 在 双氧水 作用下， 反应 14.0h， 以65%的产率得到oxysophocarpine
  参考文献：
  名称：

  Identification of UQCRB as an oxymatrine recognizing protein using a T7 phage display screen

  摘要：

  Ethnopharmacological relevance: Sophora flavescens Aiton (Radix Sophorae Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic hepatitis B (CHB), and has the ability to clear heat and dampness from the body. Oxymatrine is one of the major bioactive compounds extracted from Sophora flavescens Aiton and constitutes more than 90% of the oxymatrine injection commonly used for CHB treatment in clinics in China.Aim of the study: We aim to analyze the protein binding target of oxymatrine in treating CHB by screening a T7 phage display cDNA library of human CHB and examine the biochemistry of protein-ligand binding between oxymatrine and its ligands.Materials and methods: A T7 phage cDNA library of human CHB was biopanned by affinity selection using oxymatrine as bait. The interaction of oxymatrine with its candidate binding protein was investigated by affinity assay, molecular docking, Isothermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR).Results: A library of potential oxymatrine binding peptides was generated. Ubiquinol-cytochrome c reductase binding protein (UQCRB) was one of the candidate binding proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the oxymatrine group were significantly higher than that in the control group, biotin group, and matrine group (p < 0.05 or p < 0.01). Three-dimensional structure modeling of the UQCRB with oxymatrine showed that their binding interfaces matched and oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and G1u91. The binding affinity constant (Kb) from SPR was 4.2 mM. The Kb from ITC experiment was 3.9 mM and stoichiometry was fixed as 1, which fit very well with the result of SPR The binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as hydrogen bonds and polar interactions as the heat released was about 157 kcal/mol and Delta G was less than zero.Conclusions: In this study, using the 17 phage display system, we have identified UQCRB as a direct binding protein of oxymatrine. Furthermore, the specificity and molecular interaction of oxymatrine with UQCRB were also determined. The binding of UQCRB to oxymatrine suggests that UQCRB is a potential target of oxymatrine in treating CHB. These results provide new understanding into the mechanism of oxymatrine and insights into the strategy on the treatment of CHB. (C) 2016 Elsevier Ireland Ltd. All rights reserved.

  DOI：

  10.1016/j.jep.2016.08.007

文献信息

• An innovative extraction strategy for herbal medicine by adopting p‐sulphonatocalix[6]/[8]arenes
  作者：Xuan Yu、Teng‐hui Liang、Meng Wang、Xiao‐liang Ren、Zhen‐yu Zhou、Miao‐miao Jiang、De‐qin Zhang

  DOI：10.1002/pca.3160

  日期：2022.10

  Alkaloids exist in various herbal medicine widely and exhibit diverse biological and pharmacological activities. p-Sulphonatocalix[6]arenes (SC6A) and p-sulphonatocalix[8]arenes (SC8A) are water-soluble supramolecular macrocycles and are applied to the extraction of alkaloids from herbal products.

  生物碱广泛存在于各种草药中，具有多种生物和药理活性。p-Sulphonatocalix[6] 芳烃 (SC6A) 和 p-sulphonatocalix[8] 芳烃 (SC8A) 是水溶性超分子大环化合物，适用于从草药产品中提取生物碱。
• Identification of UQCRB as an oxymatrine recognizing protein using a T7 phage display screen
  作者：Yan-hui Sun、Xiao-yuan Zhang、Wei-qun Xie、Guang-jian Liu、Xi-xin He、Ya-li Huang、Guang-xian Zhang、Jian Wang、Zao-yuan Kuang、Ren Zhang

  DOI：10.1016/j.jep.2016.08.007

  日期：2016.12

  Ethnopharmacological relevance: Sophora flavescens Aiton (Radix Sophorae Flavescentis, Kushen) is used in traditional Chinese medicine to treat chronic hepatitis B (CHB), and has the ability to clear heat and dampness from the body. Oxymatrine is one of the major bioactive compounds extracted from Sophora flavescens Aiton and constitutes more than 90% of the oxymatrine injection commonly used for CHB treatment in clinics in China.Aim of the study: We aim to analyze the protein binding target of oxymatrine in treating CHB by screening a T7 phage display cDNA library of human CHB and examine the biochemistry of protein-ligand binding between oxymatrine and its ligands.Materials and methods: A T7 phage cDNA library of human CHB was biopanned by affinity selection using oxymatrine as bait. The interaction of oxymatrine with its candidate binding protein was investigated by affinity assay, molecular docking, Isothermal Titration Calorimetry (ITC) and Surface Plasmon Resonance (SPR).Results: A library of potential oxymatrine binding peptides was generated. Ubiquinol-cytochrome c reductase binding protein (UQCRB) was one of the candidate binding proteins of oxymatrine. UQCRB-displaying T7 phage binding numbers in the oxymatrine group were significantly higher than that in the control group, biotin group, and matrine group (p < 0.05 or p < 0.01). Three-dimensional structure modeling of the UQCRB with oxymatrine showed that their binding interfaces matched and oxymatrine inserted into a deeper pocket of UQCRB, which mainly involved amino acid residues Tyr21, Arg33, Tyr83, Glu84, Asp86, Pro88, and G1u91. The binding affinity constant (Kb) from SPR was 4.2 mM. The Kb from ITC experiment was 3.9 mM and stoichiometry was fixed as 1, which fit very well with the result of SPR The binding of oxymatrine to UQCRB was driven by strong enthalpy forces such as hydrogen bonds and polar interactions as the heat released was about 157 kcal/mol and Delta G was less than zero.Conclusions: In this study, using the 17 phage display system, we have identified UQCRB as a direct binding protein of oxymatrine. Furthermore, the specificity and molecular interaction of oxymatrine with UQCRB were also determined. The binding of UQCRB to oxymatrine suggests that UQCRB is a potential target of oxymatrine in treating CHB. These results provide new understanding into the mechanism of oxymatrine and insights into the strategy on the treatment of CHB. (C) 2016 Elsevier Ireland Ltd. All rights reserved.