5-propionyloxy-1,4-naphthoquinone | 67513-19-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-propionyloxy-1,4-naphthoquinone
• 英文别名: (5,8-Dioxonaphthalen-1-yl) propanoate
• CAS: 67513-19-3
• 化学式: C₁₃H₁₀O₄
• 分子量: 230.22
• InChiKey: MHTRQSAKBZLLJM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-羟基对萘醌 、 丙酸 在 4-二甲氨基吡啶 、 2-甲基-6-硝基苯甲酸酐 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以64%的产率得到5-propionyloxy-1,4-naphthoquinone
  参考文献：
  名称：

  Inhibitory effect of novel 5-O-acyl juglones on mammalian DNA polymerase activity, cancer cell growth and inflammatory response

  摘要：

  We previously found that vitamin K(3) (menadione, 2-methyl-1,4-naphthoquinone) inhibits the activity of human mitochondrial DNA polymerase gamma (pol gamma). In this study, we focused on juglone (5-hydroxy-1,4-naphthoquinone), which is a 1,4-naphthoquinone derivative, and chemically synthesized novel juglones conjugated with C2:0 to C22:6 fatty acid (5-O-acyl juglones). The chemically modified juglones enhanced mammalian pol inhibition and their cytotoxic and anti-inflammatory activities. The juglone conjugated with oleic acid (C18:1-acyl juglone) showed the strongest inhibition of DNA replicative pol alpha activity and human colon carcinoma (HCT116) cell growth in 10 synthesized 5-O-acyl juglones. C12:0-Acyl juglone was the strongest inhibitor of DNA repair-related pot lambda, as well as the strongest suppression of the production of tumor necrosis factor (TNF)-alpha production induced by lipopolysaccharide (LPS) in the compounds tested. Moreover, this compound caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ears. C12:0- and C18:1-Acyl juglones selectively inhibited the activities of mammalian pol species, but did not influence the activities of other pols and DNA metabolic enzymes tested. These data indicate that the novel 5-O-acyl juglones target anti-cancer and/or anti-inflammatory agents based on mammalian pot inhibition. Moreover, the results suggest that acylation of juglone is an effective chemical modification to improve the anti-cancer and anti-inflammation of vitamin K(3) derivatives, such as juglone. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.08.023

文献信息

• Discovery of juglone and its derivatives as potent SARS-CoV-2 main proteinase inhibitors
  作者：Jiahua Cui、Jinping Jia

  DOI：10.1016/j.ejmech.2021.113789

  日期：2021.12

  4-naphthoquinones with juglone skeleton were prepared and evaluated for the inhibitory efficacy against SARS-CoV-2 Mpro. More than half of the tested naphthoquinones could effectively inhibit the target enzyme with an inhibition rate of more than 90% at the concentration of 10 μM. In the structure-activity relationships (SARs) analysis, the characteristics of substituents and their position on juglone core scaffold

  SARS-CoV-2 作为一种正义单链 RNA 冠状病毒，引起了 COVID-19 的全球爆发。病毒的主要蛋白酶（M pro ）作为处理病毒多蛋白的主要酶，有助于 SARS-CoV-2 在宿主细胞中的复制和转录，并已被定性为药物发现中有吸引力的靶标。在此，制备了一组具有胡桃醌骨架的1,4-萘醌，并评估了其对 SARS-CoV-2 M pro的抑制功效。超过一半的测试萘醌能够有效抑制目标酶，在10 μM浓度下抑制率超过90%。在构效关系（SAR）分析中，取代基的特征及其在胡桃醌核心支架上的位置被认为是酶抑制活性的关键成分。最活跃的化合物 2-乙酰基-8-甲氧基-1,4-萘醌 ( 15 ) 比作为阳性对照的紫草素表现出更高的酶抑制效力，对 M pro的 IC 50值为 72.07 ± 4.84 nM -介导的荧光标记肽的水解。在分子对接研究中，它通过与相邻氨基酸残基形成氢键，很好地融入酶的活性
• Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study
  作者：Juan M. Sánchez-Calvo、Gara R. Barbero、Guillermo Guerrero-Vásquez、Alexandra G. Durán、Mariola Macías、Manuel A. Rodríguez-Iglesias、José M. G. Molinillo、Francisco A. Macías

  DOI：10.1007/s00044-016-1550-x

  日期：2016.6

  4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16 µg/mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2 µg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure–activity relationships is very important in the search

  1,4-萘醌衍生物的合成备受关注，因为这些化合物作为抗疟疾，抗菌，抗真菌和抗癌剂具有很强的活性。合成了一系列50种萘醌衍生物，并使用肉汤微稀释法评估了其对大肠杆菌，铜绿假单胞菌，粪肠球菌，金黄色葡萄球菌，克鲁斯假丝酵母，副念珠菌和新隐球菌的抗菌和抗真菌活性。该念珠菌种是最易感的微生物。1,4-萘醌的卤素衍生物具有很强的活性，例如2-溴-5-羟基-1,4-萘醌，在金黄色葡萄球菌和2-chloro-5中的MIC为16 µg / mL时表现出抑制作用，8-二羟基-1,4-萘醌，在克鲁氏梭菌中的MIC为2 µg / mL 。这些化合物显示出较高的抗真菌活性，但抗菌活性非常低。由于药库的限制，结构-活性关系的研究对于寻找新的抗微生物药物非常重要。
• Inhibitory effect of novel 5-O-acyl juglones on mammalian DNA polymerase activity, cancer cell growth and inflammatory response
  作者：Sayako Maruo、Isoko Kuriyama、Kouji Kuramochi、Kazunori Tsubaki、Hiromi Yoshida、Yoshiyuki Mizushina

  DOI：10.1016/j.bmc.2011.08.023

  日期：2011.10

  We previously found that vitamin K(3) (menadione, 2-methyl-1,4-naphthoquinone) inhibits the activity of human mitochondrial DNA polymerase gamma (pol gamma). In this study, we focused on juglone (5-hydroxy-1,4-naphthoquinone), which is a 1,4-naphthoquinone derivative, and chemically synthesized novel juglones conjugated with C2:0 to C22:6 fatty acid (5-O-acyl juglones). The chemically modified juglones enhanced mammalian pol inhibition and their cytotoxic and anti-inflammatory activities. The juglone conjugated with oleic acid (C18:1-acyl juglone) showed the strongest inhibition of DNA replicative pol alpha activity and human colon carcinoma (HCT116) cell growth in 10 synthesized 5-O-acyl juglones. C12:0-Acyl juglone was the strongest inhibitor of DNA repair-related pot lambda, as well as the strongest suppression of the production of tumor necrosis factor (TNF)-alpha production induced by lipopolysaccharide (LPS) in the compounds tested. Moreover, this compound caused the greatest reduction in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in mouse ears. C12:0- and C18:1-Acyl juglones selectively inhibited the activities of mammalian pol species, but did not influence the activities of other pols and DNA metabolic enzymes tested. These data indicate that the novel 5-O-acyl juglones target anti-cancer and/or anti-inflammatory agents based on mammalian pot inhibition. Moreover, the results suggest that acylation of juglone is an effective chemical modification to improve the anti-cancer and anti-inflammation of vitamin K(3) derivatives, such as juglone. (C) 2011 Elsevier Ltd. All rights reserved.