利福平苯醌 | 13983-13-6

• 物质功能分类: 原料药 - 抗生素类药物 - 利福霉素类药
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 中文名称: 利福平苯醌
• 中文别名: (8E,24E)-5,17,19-三羟基-23-甲氧基-2,4,12,16,18,20,22-七甲基-8-{[(4-甲基哌嗪-1-基)氨基]甲亚基}-1,6,9,11-四羰基-1,2,8,9-四氢-6H-2,7-(环氧十五碳[1,11,13]三烯桥氮烯桥)萘并[2,1-b]呋喃-21-基乙酸酯；醌式利福平
• 英文名称: rifampicin quinone
• 英文别名: Rifampin S；[(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17-trihydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-[(E)-(4-methylpiperazin-1-yl)iminomethyl]-6,23,27,29-tetraoxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(28),2,4,9,19,21,25-heptaen-13-yl] acetate
• CAS: 13983-13-6
• 化学式: C₄₃H₅₆N₄O₁₂
• 分子量: 820.937
• InChiKey: IHHAOHNZEKYBLG-WLSIYKJHSA-N

物化性质

• 熔点：
  185 °C
• 密度：
  1.34±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  59
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  214
• 氢给体数：
  4
• 氢受体数：
  15

安全信息

• WGK Germany：
  3
• 海关编码：
  2933599550

反应信息

• 作为产物：
  描述：

  rifampicin 在 horseradish peroxidase 双氧水 作用下， 以 phosphate buffer 为溶剂， 生成 利福平苯醌
  参考文献：
  名称：

  Horseradish Peroxidase-Catalyzed Oxidation of Rifampicin: Reaction Rate Enhancement by Co-oxidation with Anti-inflammatory Drugs

  摘要：

  抗结核药物利福平被描述为活性物质的清除剂。此外，最近的研究表明，在实验性麻风病动物模型中，利福平和辣根过氧化物酶 (HRP) 复合物的口服治疗比单独使用利福平更有效，这表明涉及利福平的氧化还原反应的重要性及其与作用机制的相关性。因此，我们研究了 HRP 催化的利福平氧化，因为这种酶可能代表过氧化介导反应的原型。我们发现抗生素被有效氧化，并且产物是利福平醌，该反应依赖于 HRP 和过氧化氢。测量稳态动力学常数Kmapp (101±23 μmol/l)、Vmaxapp (0.78±0.09 μmol/l·s−1) 和kcat (5.1±0.6 s−1) (n=4)。通过添加共底物如四甲基联苯胺、水杨酸、5-氨基水杨酸和对乙酰氨基酚来提高反应速率。这种效应可以通过电子转移机制来解释，这些药物通过该机制充当利福平氧化的介质。我们认为这种药物相互作用可能在炎症部位很重要。

  DOI：

  10.1248/bpb.28.1822

文献信息

• US8404664B2
  申请人：——

  公开号：US8404664B2

  公开（公告）日：2013-03-26
• US8524691B2
  申请人：——

  公开号：US8524691B2

  公开（公告）日：2013-09-03
• Environmentally Friendly Degradation and Detoxification of Rifampicin by a Bacterial Laccase and Hydrogen Peroxide
  作者：Paulo Durão、Peter Kis、Ivo M. Chelo、M. Rita Ventura、Lígia O. Martins

  DOI：10.1002/cbic.202300627

  日期：2024.1.15

  Antibiotics are micropollutants accumulating in our rivers and wastewaters, potentially leading to bacterial antibiotic resistance, a worldwide problem to which there is no current solution. Here, we have developed an environmentally friendly two‐step process to transform the antibiotic rifampicin (RIF) into non‐antimicrobial compounds. The process involves an enzymatic oxidation step by the bacterial CotA‐laccase and a hydrogen peroxide bleaching step. NMR identified rifampicin quinone as the main product of the enzymatic oxidation. Growth of Escherichia coli strains in the presence of final degradation products (FP) and minimum inhibitory concentration (MIC) measurements confirmed that FP are non‐anti‐microbial compounds, and bioassays suggest that FP is not toxic to eukaryotic organisms. Moreover, competitive fitness assays between susceptible and RIF‐resistant bacteria show that susceptible bacteria is strongly favoured in the presence of FP. Our results show that we have developed a robust and environmentally friendly process to effectively remediate rifampicin from antibiotic contaminated environments.
• Horseradish Peroxidase-Catalyzed Oxidation of Rifampicin: Reaction Rate Enhancement by Co-oxidation with Anti-inflammatory Drugs
  作者：Fernanda de Jesus Notário dos Santos、Valdecir Farias Ximenes、Luiz Marcos da Fonseca、Olga Maria Mascarenhas de Faria Oliveira、Iguatemy Lourenço Brunetti

  DOI：10.1248/bpb.28.1822

  日期：——

  The tuberculostatic drug rifampicin has been described as a scavenger of reactive species. Additionally, the recent demonstration that oral therapy with a complex of rifampicin and horseradish peroxidase (HRP) was more effective than rifampicin alone, in an animal model of experimental leprosy, suggested the importance of redox reactions involving rifampicin and their relevance to the mechanism of action. Hence, we studied the oxidation of rifampicin catalyzed by HRP, since this enzyme may represent the prototype of peroxidation-mediated reactions. We found that the antibiotic is efficiently oxidized and that rifampicin-quinone is the product, in a reaction dependent on both HRP and hydrogen peroxide. The steady-state kinetic constants Kmapp (101±23 μmol/l), Vmaxapp (0.78±0.09 μmol/l·s−1) and kcat (5.1±0.6 s−1) were measured (n=4). The reaction rate was increased by the addition of co-substrates such as tetramethylbenzidine, salicylic acid, 5-aminosalicylic acid and paracetamol. This effect was explained by invoking an electron-transfer mechanism by which these drugs acted as mediators of rifampicin oxidation. We suggested that this drug interaction might be important at the inflammatory site.

  抗结核药物利福平被描述为活性物质的清除剂。此外，最近的研究表明，在实验性麻风病动物模型中，利福平和辣根过氧化物酶 (HRP) 复合物的口服治疗比单独使用利福平更有效，这表明涉及利福平的氧化还原反应的重要性及其与作用机制的相关性。因此，我们研究了 HRP 催化的利福平氧化，因为这种酶可能代表过氧化介导反应的原型。我们发现抗生素被有效氧化，并且产物是利福平醌，该反应依赖于 HRP 和过氧化氢。测量稳态动力学常数Kmapp (101±23 μmol/l)、Vmaxapp (0.78±0.09 μmol/l·s−1) 和kcat (5.1±0.6 s−1) (n=4)。通过添加共底物如四甲基联苯胺、水杨酸、5-氨基水杨酸和对乙酰氨基酚来提高反应速率。这种效应可以通过电子转移机制来解释，这些药物通过该机制充当利福平氧化的介质。我们认为这种药物相互作用可能在炎症部位很重要。