2-(4-bromophenyl)-5,7-dihydroxy-6-methoxy-4H-chromen-4-one | 1637569-02-8

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 2-(4-bromophenyl)-5,7-dihydroxy-6-methoxy-4H-chromen-4-one
• 英文别名: 2-(4-Bromophenyl)-5,7-dihydroxy-6-methoxychromen-4-one；2-(4-bromophenyl)-5,7-dihydroxy-6-methoxychromen-4-one
• CAS: 1637569-02-8
• 化学式: C₁₆H₁₁BrO₅
• 分子量: 363.164
• InChiKey: NUCBTEHZHSADSU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  76
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-bromophenyl)-5,7-dihydroxy-6-methoxy-4H-chromen-4-one 、 3-丁炔-1-醇 在 [1,1'-binaphthalen]-2-yldibutylplatinum 、 palladium diacetate 、 caesium carbonate 作用下， 以 乙二醇二甲醚 为溶剂， 反应 10.0h， 以41%的产率得到2-(4-(but-3-yn-1-yloxy)phenyl)-5,7-dihydroxy-6-methoxy-4H-chromen-4-one
  参考文献：
  名称：

  Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates

  摘要：

  Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action have remained elusive. Using a high-throughput assay for type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting bacterial growth. Among the active TCMs, we discovered that baicalein, a specific flavonoid from Scutellaria baicalensis, targets S. Typhimurium pathogenicity island-1 (SPI-1) type III secretion system (T3SS) effectors and translocases to inhibit bacterial invasion of epithelial cells. Structurally related flavonoids present in other TCMs, such as quercetin, also inactivated the SPI-1 T3SS and attenuated S. Typhimurium invasion. Our results demonstrate that specific plant metabolites from TCMs can directly interfere with key bacterial virulence pathways and reveal a previously unappreciated mechanism of action for anti-infective medicinal plants.

  DOI：

  10.1021/jacs.5b11575
• 作为产物：
  描述：

  3,4,5-三甲氧基苯酚 在 三氟化硼乙醚 、 水 、 氢溴酸 、 碘 、 四丁基碘化铵 、 potassium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 14.0h， 生成 2-(4-bromophenyl)-5,7-dihydroxy-6-methoxy-4H-chromen-4-one
  参考文献：
  名称：

  Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates

  摘要：

  Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action have remained elusive. Using a high-throughput assay for type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting bacterial growth. Among the active TCMs, we discovered that baicalein, a specific flavonoid from Scutellaria baicalensis, targets S. Typhimurium pathogenicity island-1 (SPI-1) type III secretion system (T3SS) effectors and translocases to inhibit bacterial invasion of epithelial cells. Structurally related flavonoids present in other TCMs, such as quercetin, also inactivated the SPI-1 T3SS and attenuated S. Typhimurium invasion. Our results demonstrate that specific plant metabolites from TCMs can directly interfere with key bacterial virulence pathways and reveal a previously unappreciated mechanism of action for anti-infective medicinal plants.

  DOI：

  10.1021/jacs.5b11575

文献信息

• Synthesis and Anti-influenza Activities of Novel Baicalein Analogs
  作者：Shu-Ting Chung、Pei-Yu Chien、Wen-Hsin Huang、Chen-Wen Yao、An-Rong Lee

  DOI：10.1248/cpb.c13-00897

  日期：——

  A series of novel flavones derivatives were synthesized based on modification of the active ingredients of a traditional Chinese medicine Scutellaria baicalensis GEORGI and screened for anti-influenza activity. The synthetic baicalein (flavone) analogs, especially with the B-rings substituted with bromine atoms, were much more potent than oseltamivir or ribavirin against H1N1 Tamiflu-resistant (H1N1 TR) virus and usually with more favorable selectivity. The most promising were 5b, 5c, 6b and 6c, all displaying an 50% effective concentration (EC50) at around 4.0–4.5 µM, and a selective index (SI=50% cytotoxic concentration (CC50)/EC50)>70. For seasonal H3N2-infected influenza virus, both 5a and 5b with SI >17.3 indicated superior to ribavirin. The flavonoids having both not-naturally-occurring bromo-substituted B-rings and appropriate hydroxyls positioning on the A-rings might be critical in determining the activity and selectivity against H1N1-Tamiflu-resistant infected influenza viruses.

  一系列新型黄酮衍生物是基于对传统中药黄芩（Scutellaria baicalensis GEORGI）活性成分的修饰合成的，并进行了抗流感活性筛选。合成的大黄素（黄酮）类似物，特别是B环上带有溴原子取代的类似物，对H1N1达菲耐药（H1N1 TR）病毒的活性远超奥司他韦或利巴韦林，并且通常具有更优越的选择性。最有希望的化合物是5b、5c、6b和6c，它们的50%有效浓度（EC50）都在4.0–4.5 µM左右，选择指数（SI=50%细胞毒性浓度（CC50）/EC50）>70。对于季节性H3N2流感病毒感染，5a和5b的SI均大于17.3，优于利巴韦林。这些具有非天然溴取代B环和A环上适当羟基位置的黄酮类化合物可能在决定抗H1N1达菲耐药流感病毒的活性和选择性方面起关键作用。
• COMPOSITION AND METHOD FOR TREATING OR PREVENTING INFLUENZA VIRUS INFECTION
  申请人：National Defense Medical Center

  公开号：US20150329515A1

  公开（公告）日：2015-11-19

  The present invention provides a pharmaceutical composition and method for treating or preventing influenza virus infection in a subject comprising administering the subject with a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of compounds provided in this invention. In addition, the prevent invention provides new compounds for treating or preventing influenza virus infection.

  本发明提供了一种治疗或预防流感病毒感染的药物组合物和方法，包括向受试者施用包含本发明提供的化合物的药物组合物，其中该药物组合物包括一种药用可接受载体和治疗有效量的化合物。此外，本发明还提供了用于治疗或预防流感病毒感染的新化合物。
• Antibacterial Flavonoids from Medicinal Plants Covalently Inactivate Type III Protein Secretion Substrates
  作者：Lun K. Tsou、María Lara-Tejero、Jordan RoseFigura、Zhenrun J. Zhang、Yen-Chih Wang、Jacob S. Yount、Matthew Lefebre、Paul D. Dossa、Junya Kato、Fulan Guan、Wing Lam、Yung-Chi Cheng、Jorge E. Galán、Howard C. Hang

  DOI：10.1021/jacs.5b11575

  日期：2016.2.24

  Traditional Chinese Medicines (TCMs) have been historically used to treat bacterial infections. However, the molecules responsible for these anti-infective properties and their potential mechanisms of action have remained elusive. Using a high-throughput assay for type III protein secretion in Salmonella enterica serovar Typhimurium, we discovered that several TCMs can attenuate this key virulence pathway without affecting bacterial growth. Among the active TCMs, we discovered that baicalein, a specific flavonoid from Scutellaria baicalensis, targets S. Typhimurium pathogenicity island-1 (SPI-1) type III secretion system (T3SS) effectors and translocases to inhibit bacterial invasion of epithelial cells. Structurally related flavonoids present in other TCMs, such as quercetin, also inactivated the SPI-1 T3SS and attenuated S. Typhimurium invasion. Our results demonstrate that specific plant metabolites from TCMs can directly interfere with key bacterial virulence pathways and reveal a previously unappreciated mechanism of action for anti-infective medicinal plants.