acetylsalicylate | 5054-56-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: acetylsalicylate
• 英文别名: 2-acetyloxybenzoate
• CAS: 5054-56-8
• 化学式: C₉H₇O₄
• 分子量: 179.152
• InChiKey: BSYNRYMUTXBXSQ-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  66.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  acetylsalicylate 在 (2-) 作用下， 以 水 为溶剂， 生成
  参考文献：
  名称：

  Osmium(VIII) catalysed and uncatalysed oxidation of aspirin drug by diperiodatocuprate(III) complex in aqueous alkaline medium: A mechanistic approach

  摘要：

  The kinetics of oxidation of a non-steroidal analgesic drug, aspirin (ASP) by diperiodatocuprate(III)(DPC) in the presence and absence of osmium(VIII) have been investigated at 298 K in alkaline medium at a constant ionic strength of 0.10 mol dm(-3) spectrophotometrically. The reaction showed a first-order in DPC] and less than unit order in [ASP] and [alkali] for both the osmium(VIII) catalysed and uncatalysed reactions. The order with respect to Os(VIII) concentration was unity. The effects of added products, ionic strength, periodate and dielectric constant have been studied. The stoichiometry of the reaction was found to be 1:4 (ASP:DPC) for both the cases. The main oxidation product of aspirin was identified by spot test, IR, NMR and GC-MS. The reaction constants involved in the different steps of the mechanisms were calculated for both reactions. Activation parameters with respect to slow step of the mechanisms were computed and discussed for both the cases. The thermodynamic quantities were also determined for both reactions. The catalytic constant (K-C) was also calculated for catalysed reaction at different temperatures and the corresponding activation parameters were determined. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2010.01.014
• 作为产物：
  描述：

  以 水 为溶剂， 生成 acetylsalicylate
  参考文献：
  名称：

  Osmium(VIII) catalysed and uncatalysed oxidation of aspirin drug by diperiodatocuprate(III) complex in aqueous alkaline medium: A mechanistic approach

  摘要：

  The kinetics of oxidation of a non-steroidal analgesic drug, aspirin (ASP) by diperiodatocuprate(III)(DPC) in the presence and absence of osmium(VIII) have been investigated at 298 K in alkaline medium at a constant ionic strength of 0.10 mol dm(-3) spectrophotometrically. The reaction showed a first-order in DPC] and less than unit order in [ASP] and [alkali] for both the osmium(VIII) catalysed and uncatalysed reactions. The order with respect to Os(VIII) concentration was unity. The effects of added products, ionic strength, periodate and dielectric constant have been studied. The stoichiometry of the reaction was found to be 1:4 (ASP:DPC) for both the cases. The main oxidation product of aspirin was identified by spot test, IR, NMR and GC-MS. The reaction constants involved in the different steps of the mechanisms were calculated for both reactions. Activation parameters with respect to slow step of the mechanisms were computed and discussed for both the cases. The thermodynamic quantities were also determined for both reactions. The catalytic constant (K-C) was also calculated for catalysed reaction at different temperatures and the corresponding activation parameters were determined. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.poly.2010.01.014

文献信息

• Tri-substituted aluminum salts or di-substituted aluminum salts of
  申请人：Teikoku Hormone Mfg. Co., Ltd.

  公开号：US03988333A1

  公开（公告）日：1976-10-26

  A process for the preparation of di- or tri-substituted aluminum salts of carboxyl group-containing, pharmaceutically effective compounds which comprises reacting up to three types of carboxyl group-containing, pharmaceutically effective compounds with an organic aluminum compound expressed by the following formula; ##EQU1## wherein R.sub.1 and R.sub.2, which may be the same or different, stand for an aliphatic, alicyclic or aromatic hydrocarbon residue having up to 10 carbon atoms, and R.sub.3 stands for a hydrocarbon residue as defined with respect to R.sub.1 and R.sub.2, which may be the same as, or different from, R.sub.1 and R.sub.2, or a hydrocarbyloxy group of the formula OR.sub.4 in which R.sub.4 is an aliphatic, alicyclic or aromatic hydrocarbon residue having up to 10 carbon atoms, and a novel di- or tri-substituted aluminum salts of carboxyl group-containing, pharmaceutically effective compounds.

  一种制备含羧基、具有药物活性的二或三取代铝盐的工艺，包括将最多三种含羧基、具有药物活性的化合物与下式表示的有机铝化合物反应：##EQU1## 其中R.sub.1和R.sub.2，可能相同或不同，代表具有最多10个碳原子的脂肪族、环烷或芳香烃碳氢基团，而R.sub.3代表与R.sub.1和R.sub.2相同或不同的具有上述定义的碳氢基团，或者是具有最多10个碳原子的脂肪族、环烷或芳香烃碳氢基团的羟基烷氧基团OR.sub.4，从而得到一种新型的含羧基、具有药物活性的二或三取代铝盐。
• Aspirin hydrolyzing esterases from rat liver cytosol
  作者：Dong-Hyun Kim、Yuh-Shyong Yang、William B. Jakoby

  DOI：10.1016/0006-2952(90)90546-w

  日期：1990.8

  Unlike most esterases, which are predominantly bound to the microsomal fraction, the enzymes hydrolyzing acetylsalicylic acid are present in an equal amount in the cytosol. Two soluble isozymes were purified to homogeneity from rat liver and characterized as serine esterases with a Mr of 35,000. Both had the wide substrate spectrum characteristic of enzymes active in detoxication. Both had a very low

  与大多数主要与微粒体部分结合的酯酶不同，水解乙酰水杨酸的酶以等量存在于细胞质中。从大鼠肝脏中纯化了两种可溶性同工酶，使其均质，其特征在于丝氨酸酯酶的Mr值为35,000。两者均具有脱毒活性酶的宽底物光谱特征。两者对于乙酰水杨酸酯的Km都非常低。观察到了三种其他具有阿司匹林活性的细胞质酶，但它们的高Mr（约220,000）和与一种均质同工酶的抗体缺乏反应性有所不同。
• Partial purification and characterization of a microsomal carboxylesterase specific for salicylate esters from guinea-pig liver
  作者：Kenneth N. White、Derek B. Hope

  DOI：10.1016/0167-4838(84)90138-9

  日期：1984.3

  work describes its partial purification and characterization. The enzyme is monomeric, it has a molecular weight of approx. 55 000 and is very sensitive to inhibition by the carboxylesterase inhibitor bis(4-nitrophenyl)phosphate. Although it could not be completely separated from contaminating carboxylesterases, substrate specificity was investigated using the negatively charged esters of salicylic acid

  肝羧酸酯酶的研究主要涉及使用不带电荷的酯和酰胺底物来监测活性。已经鉴定了来自豚鼠肝微粒体的微粒体羧酸酯酶（EC 3.1.1.1），其特异性水解阿司匹林（White，KN and Hope，DB（1981）Biochem。J. 197，771-773），该底物带负电。在生理pH值下，该工作描述了其部分纯化和表征。该酶是单体的，它的分子量约为1。55000，并且对羧酸酯酶抑制剂双（4-硝基苯基）磷酸酯的抑制非常敏感。尽管不能完全将其与污染的羧酸酯酶分离，但使用水杨酸带负电荷的酯研究了底物特异性。该酶对水杨酸的乙酰酯阿司匹林不是特异的，但是可以更快地水解较长链的酯，正辛酰基酯的Vmax最高。对该酶进行底物抑制，其随酯上脂肪酸链长的增加而增加，并且在低于临界胶束浓度的底物浓度下达到100％抑制。
• Aspirin acetylates wild type and mutant p53 in colon cancer cells: identification of aspirin acetylated sites on recombinant p53
  作者：Guoqiang Ai、Rakesh Dachineni、D. Ramesh Kumar、Srinivasan Marimuthu、Lloyd F. Alfonso、G. Jayarama Bhat

  DOI：10.1007/s13277-015-4438-3

  日期：2016.5

  Aspirin’s ability to inhibit cell proliferation and induce apoptosis in cancer cell lines is considered to be an important mechanism for its anti-cancer effects. We previously demonstrated that aspirin acetylated the tumor suppressor protein p53 at lysine 382 in MDA-MB-231 human breast cancer cells. Here, we extended these observations to human colon cancer cells, HCT 116 harboring wild type p53, and HT-29 containing mutant p53. We demonstrate that aspirin induced acetylation of p53 in both cell lines in a concentration-dependent manner. Aspirin-acetylated p53 was localized to the nucleus. In both cell lines, aspirin induced p21CIP1. Aspirin also acetylated recombinant p53 (rp53) in vitro suggesting that it occurs through a non-enzymatic chemical reaction. Mass spectrometry analysis and immunoblotting identified 10 acetylated lysines on rp53, and molecular modeling showed that all lysines targeted by aspirin are surface exposed. Five of these lysines are localized to the DNA-binding domain, four to the nuclear localization signal domain, and one to the C-terminal regulatory domain. Our results suggest that aspirin’s anti-cancer effect may involve acetylation and activation of wild type and mutant p53 and induction of target gene expression. This is the first report attempting to characterize p53 acetylation sites targeted by aspirin.

  阿司匹林抑制癌细胞增殖和诱导癌细胞凋亡的能力被认为是其抗癌作用的重要机制。我们之前已经证明，阿司匹林在MDA-MB-231人乳腺癌细胞中乙酰化抑癌蛋白p53的赖氨酸382。在此，我们将这些观察结果扩展到人类结肠癌细胞，即携带野生型p53的HCT 116和含有突变型p53的HT-29。我们证明，阿司匹林以浓度依赖的方式诱导两种细胞系中p53的乙酰化。阿司匹林乙酰化的p53定位于细胞核。在这两种细胞系中，阿司匹林诱导p21CIP1。阿司匹林还在体外乙酰化重组p53（rp53），表明其通过非酶促化学反应发生。质谱分析和免疫印迹鉴定出rp53上有10个乙酰化的赖氨酸，分子建模显示，阿司匹林靶向的所有赖氨酸都是表面暴露的。其中5个赖氨酸定位于DNA结合域，4个定位于核定位信号域，1个定位于C端调节域。我们的结果表明，阿司匹林的抗癌作用可能涉及野生型和突变型p53的乙酰化和激活以及靶基因表达的诱导。这是首次尝试描述阿司匹林靶向的p53乙酰化位点的报告。
• Mechanistic Insights into a Classic Wonder Drug—Aspirin
  作者：Jinping Lei、Yanzi Zhou、Daiqian Xie、Yingkai Zhang

  DOI：10.1021/ja5112964

  日期：2015.1.14

  Aspirin, one of the oldest and most common anti-inflammatory agents, has recently been shown to reduce cancer risks. The principal pharmacological effects of aspirin are known to arise from its covalent modification of cyclooxygenase-2 (COX-2) through acetylation of Ser530, but the detailed mechanism of its biochemical action and specificity remains to be elucidated. In this work, we have filled this

  阿司匹林是最古老和最常见的抗炎药之一，最近被证明可以降低癌症风险。已知阿司匹林的主要药理作用源自其通过 Ser530 乙酰化对环氧合酶 2 (COX-2) 的共价修饰，但其生化作用和特异性的详细机制仍有待阐明。在这项工作中，我们通过采用最先进的计算方法、具有从头计算量子力学/分子力学势和伞采样的玻恩-奥本海默分子动力学模拟来填补了这一空白。我们的研究描述了阿司匹林乙酰化COX的底物辅助抑制机制：它以亚稳态四面体中间体分两个连续阶段进行，其中阿司匹林的羧基作为通用碱基。计算结果证实阿司匹林对 COX-1 的效力比对 COX-2 的效力强 10-100 倍，并揭示两种 COX 异构体之间的这种抑制特异性主要归因于共价抑制反应动力学速率的差异，而不是阿司匹林结合步骤。阿司匹林对 COX 酶的这种差异性抑制的结构起源也已被阐明。