短叶苏木酚酸甲酯 | 154702-76-8

• 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 - 异香豆素及其衍生物
• 中文名称: 短叶苏木酚酸甲酯
• 英文名称: methyl brevifolincarboxylate
• 英文别名: methyl 7,8,9-trihydroxy-3,5-dioxo-1,2-dihydrocyclopenta[c]isochromene-1-carboxylate
• CAS: 154702-76-8
• 化学式: C₁₄H₁₀O₈
• 分子量: 306.229
• InChiKey: JNWDNAASYHRXMG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  130
• 氢给体数：
  3
• 氢受体数：
  8

制备方法与用途

概述

短叶苏木酚酸甲酯（methyl brevifolincarboxylate）的CAS号为154702-76-8。这种化合物从青果中提取而来，而青果是橄榄科橄榄属植物橄榄[Canarium album (Lour.) Raeusch]的果实。青果收录于2015版《中国药典》，常用于治疗咽喉肿痛、咳嗽、烦渴及鱼蟹中毒等症状。已有文献表明，短叶苏木酚酸甲酯具有抑制人单纯疱疹病毒HSV-1 STAKER株和HSV-2 SAR株的活性、抑制血小板凝集以及舒张血管的作用。

制备

提取短叶苏木酚酸甲酯的方法如下：取干燥的叶下珠全草，打成粗粉后置入索氏提取器中。首先用石油醚脱脂，将药渣晾干后再用甲醇充分提取。分出甲醇提取液，并通过减压蒸馏浓缩得到甲醇浸膏。随后，将此浸膏加适量水混悬，依次以氯仿及正丁醇分配。取出正丁醇部分后进行减压浓缩，再以硅胶及硅藻土拌料制成柱层析材料。使用氯仿-甲醇-水作为梯度洗脱剂进行硅胶低压柱层析，收集第36份起的洗脱液（每份250毫升），从而得到粗品短叶苏木酚酸甲酯。该粗制品再经过二次纯化，用甲醇-氯仿重结晶后即得纯短叶苏木酚酸甲酯。

生物活性

短叶苏木酚酸甲酯是一种有效的流感病毒 PB2 帽结合抑制剂，对流感病毒 A/Puerto Rico/8/34 (H1N1) 和 A/Aichi/2/68 (H3N2) 具有抑制作用，其IC50值分别为27.16 μM和33.41 μM。此外，它还表现出显著的抗氧化活性。

体外研究

短叶苏木酚酸甲酯展现出明显的DPPH自由基清除能力，IC50值为8.9 μM。

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 短叶苏木酚酸甲酯 以30 mg的产率得到methyl tri-O-methylbrevifolincarboxylate
  参考文献：
  名称：

  Selective inactivation of triosephosphate isomerase from Trypanosoma cruzi by brevifolin carboxylate derivatives isolated from Geranium bellum Rose

  摘要：

  In the search of molecules that can serve as leads in the design of a new drug for the treatment of Chagas' disease, we found that some brevifolin carboxylate derivatives isolated from Geranium bellum Rose, inactivate triosephosphate isomerase from Trypanosoma cruzi (TcTIM) in a species-specific manner. After spectroscopic characterization, these compounds were identified as methylbrevifolin carboxylate (1), ethylbrevifolin carboxylate (2), butylbrevifolin carboxylate (3) and the methylated derivate methyl tri-O-methylbrevifolin carboxylate (4). The concentrations required to inactivate fifty percent the activity of TcTIM were 6.5, 8 and 14 mu M of 1, 2 and 3, respectively, while compound 4 had no inhibitory effect. Molecular docking simulations of 1 on the structure of TcTIM showed that residues of both monomers interact with the compound. These compounds are very selective with respect to the parasite enzyme, since they showed no effect on the activity of human TIM at concentrations as high as 1 mM. In conclusion, the brevifolin carboxylate derivatives described here are excellent leads in the search of a new chemotherapy for the treatment of this disease. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.055

文献信息

• Selective inactivation of triosephosphate isomerase from Trypanosoma cruzi by brevifolin carboxylate derivatives isolated from Geranium bellum Rose
  作者：Juan Gayosso-De-Lucio、Martin Torres-Valencia、Arturo Rojo-Domínguez、Hugo Nájera-Peña、Beatriz Aguirre-López、José Salas-Pacheco、Claudia Avitia-Domínguez、Alfredo Téllez-Valencia

  DOI：10.1016/j.bmcl.2009.08.055

  日期：2009.10

  In the search of molecules that can serve as leads in the design of a new drug for the treatment of Chagas' disease, we found that some brevifolin carboxylate derivatives isolated from Geranium bellum Rose, inactivate triosephosphate isomerase from Trypanosoma cruzi (TcTIM) in a species-specific manner. After spectroscopic characterization, these compounds were identified as methylbrevifolin carboxylate (1), ethylbrevifolin carboxylate (2), butylbrevifolin carboxylate (3) and the methylated derivate methyl tri-O-methylbrevifolin carboxylate (4). The concentrations required to inactivate fifty percent the activity of TcTIM were 6.5, 8 and 14 mu M of 1, 2 and 3, respectively, while compound 4 had no inhibitory effect. Molecular docking simulations of 1 on the structure of TcTIM showed that residues of both monomers interact with the compound. These compounds are very selective with respect to the parasite enzyme, since they showed no effect on the activity of human TIM at concentrations as high as 1 mM. In conclusion, the brevifolin carboxylate derivatives described here are excellent leads in the search of a new chemotherapy for the treatment of this disease. (C) 2009 Elsevier Ltd. All rights reserved.