3,6-diamyl-2,5-dihydroxy-1,4-benzoquinone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3,6-diamyl-2,5-dihydroxy-1,4-benzoquinone
• 英文别名: 2,5-dihydroxy-3,6-dipentyl-[1,4]benzoquinone；2,5-Dihydroxy-3,6-dipentyl-[1,4]benzochinon；2,5-Dihydroxy-3,6-dipentylcyclohexa-2,5-diene-1,4-dione；2,5-dihydroxy-3,6-dipentylcyclohexa-2,5-diene-1,4-dione
• 化学式: C₁₆H₂₄O₄
• 分子量: 280.364
• InChiKey: ZUEUCLHTSSEFQG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  74.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2,5-二羟基-1,4-苯喹酮 在 盐酸 、 正丁基锂 、 palladium 10% on activated carbon 、 氢气 、 4-甲基苯磺酸吡啶 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 正己烷 、 水 、 甲苯 为溶剂， -10.0~25.0 ℃ 、500.01 kPa 条件下， 反应 95.67h， 生成 3,6-diamyl-2,5-dihydroxy-1,4-benzoquinone
  参考文献：
  名称：

  Design, synthesis, and SAR of embelin analogues as the inhibitors of PAI-1 (plasminogen activator inhibitor-1)

  摘要：

  The natural product embelin was found to have PAI-1 inhibitory activity with the IC50 value of 4.94 mu M. Based on the structure of embelin, a series of analogues were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The SAR study on these compounds disclosed that the inhibitory potency largely depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the IC50 value of 0.18 mu M. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.045

文献信息

• Discovery of a novel inhibitor of NAD(P)+-dependent malic enzyme (ME2) by high-throughput screening
  作者：Yi Wen、Lei Xu、Fang-lei Chen、Jing Gao、Jing-ya Li、Li-hong Hu、Jia Li

  DOI：10.1038/aps.2013.189

  日期：2014.5

  Malic enzymes are oxidative decarboxylases with NAD+ or NAD(P)+ as cofactor that catalyze the conversion of L-malate to pyruvate and CO2. The aim of this study was to discover and characterize a potent inhibitor of human NAD(P)+-dependent malic enzyme 2 (ME2). Recombinant human ME2-His-Tag fusion protein was overexpressed in E coli and purified with Ni-NTA resin. A high-throughput screening (HTS) assay was developed to find ME2 inhibitors. Detergent Brij-35 was used to exclude false positives. The characteristics of the inhibitor were analyzed with enzyme kinetics analysis. A thermal shift assay for ME2 was carried out to verify the binding of the inhibitor with the enzyme. An HTS system for discovering ME2 inhibitors was established with a Z′ factor value of 0.775 and a signal-to-noise ratio (S/N) of 9.80. A library containing 12 683 natural products was screened. From 47 hits, NPD387 was identified as an inhibitor of ME2. The primary structure-activity relationship study on NPD387 derivatives showed that one derivative NPD389 was more potent than the parent compound NPD387 (the IC50 of NPD389 was 4.63±0.36 μmol/L or 5.59±0.38 μmol/L, respectively, in the absence or presence of 0.01% Brij-35 in the assay system). The enzyme kinetics analysis showed that NPD389 was a fast-binding uncompetitive inhibitor with respect to the substrate NAD+ and a mixed-type inhibitor with respect to the substrate L-malate. NPD389 is a potent ME2 inhibitor that binds to the enzyme in a fast-binding mode, acting as an uncompetitive inhibitor with respect to the substrate NAD+ and a mixed-type inhibitor with respect to the substrate L-malate.

  苹果酸酶是以NAD+或NAD(P)+为辅助因子的氧化脱羧酶，催化L-苹果酸转化为丙酮酸和二氧化碳。本研究的目的是发现并表征人类NAD(P)+依赖的苹果酸酶2（ME2）的有效抑制剂。重组人ME2-His-Tag融合蛋白在大肠杆菌中过表达，并用Ni-NTA树脂纯化。开发了高通量筛选（HTS）分析以寻找ME2抑制剂。使用洗涤剂Brij-35以排除假阳性。通过酶动力学分析分析了抑制剂的特性。对ME2进行了热转变实验，以验证抑制剂与酶的结合。建立了发现ME2抑制剂的HTS系统，Z'因子值为0.775，信噪比（S/N）为9.80。筛选了包含12683种天然产物的文库。最终，从47个命中中识别出NPD387作为ME2的抑制剂。对NPD387衍生物的初步结构-活性关系研究显示，衍生物NPD389的效能优于母化合物NPD387（NPD389在无0.01% Brij-35和有0.01% Brij-35的实验体系中的IC50分别为4.63±0.36 μmol/L和5.59±0.38 μmol/L）。酶动力学分析显示NPD389对于底物NAD+是一种快速结合的非竞争抑制剂，对于底物L-苹果酸则是一种混合型抑制剂。NPD389是一种有效的ME2抑制剂，以快速结合的方式与酶结合，作为对底物NAD+的非竞争抑制剂和对底物L-苹果酸的混合型抑制剂。
• Fichter; Jetzer; Leepin, Justus Liebigs Annalen der Chemie, 1913, vol. 395, p. 12
  作者：Fichter、Jetzer、Leepin

  DOI：——

  日期：——
• Design, synthesis, and SAR of embelin analogues as the inhibitors of PAI-1 (plasminogen activator inhibitor-1)
  作者：Fanglei Chen、Guiping Zhang、Zebin Hong、Zhonghui Lin、Min Lei、Mingdong Huang、Lihong Hu

  DOI：10.1016/j.bmcl.2014.03.045

  日期：2014.5

  The natural product embelin was found to have PAI-1 inhibitory activity with the IC50 value of 4.94 mu M. Based on the structure of embelin, a series of analogues were designed, synthesized, and evaluated for their ability to inhibit PAI-1. The SAR study on these compounds disclosed that the inhibitory potency largely depended on the hydroxyl groups at C2 and C5, and the length of the alkyl chains at C3 and C6. Compound 11 displayed the best PAI-1 inhibitory potency with the IC50 value of 0.18 mu M. (C) 2014 Elsevier Ltd. All rights reserved.