(2E)-3-(3,5-dimethoxyphenyl)-1-(3-hydroxynaphthalen-2-yl)prop-2-en-1-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (2E)-3-(3,5-dimethoxyphenyl)-1-(3-hydroxynaphthalen-2-yl)prop-2-en-1-one
• 英文别名: (E)-3-(3,5-dimethoxyphenyl)-1-(3-hydroxynaphthalen-2-yl)prop-2-en-1-one
• 化学式: C₂₁H₁₈O₄
• 分子量: 334.372
• InChiKey: UMDLLOCJSOPRAX-BQYQJAHWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2E)-3-(3,5-dimethoxyphenyl)-1-(3-hydroxynaphthalen-2-yl)prop-2-en-1-one 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 生成 (2E)-3-(3,5-dihydroxyphenyl)-1-(3-hydroxynaphthalen-2-yl)prop-2-en-1-one
  参考文献：
  名称：

  Development of hydroxylated naphthylchalcones as polyphenol oxidase inhibitors: Synthesis, biochemistry and molecular docking studies

  摘要：

  Polyphenol oxidase (Tyrosinase) has received great attention, since it is the key enzyme in melanin biosynthesis. In this study, novel hydroxy naphthylchalcone compounds were synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. The structures of the compounds synthesized were confirmed by H-1 NMR, C-13 NMR, FTIR and HRMS. Two of the compounds synthesized inhibited the diphenolase activity of tyrosinase in a dose dependent manner and exhibited much higher tyrosinase inhibitory activities (IC50 values of 10.4 mu M and 14.4 mu M, respectively) than the positive control, kojic acid (IC50: 27.5 mu M). Kinetic analysis showed that their inhibition was reversible. Both the novel compounds displayed competitive inhibition with their K-i values of 3.8 mu M and 4.5 mu M, respectively. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues. This study suggests hydroxy naphthylchalcone compounds to serve as promising candidates for use as depigmentation agents. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2015.10.003
• 作为产物：
  描述：

  1-(3-羟基萘-2-基)乙酮 、 3,5-二甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 (2E)-3-(3,5-dimethoxyphenyl)-1-(3-hydroxynaphthalen-2-yl)prop-2-en-1-one
  参考文献：
  名称：

  Integrated kinetic studies and computational analysis on naphthyl chalcones as mushroom tyrosinase inhibitors

  摘要：

  Melanin helps to protect skin from the damaging ultraviolet radiation of the sun. Tyrosinase, the key enzyme in melanogenesis is responsible for coloration of skin, hair and eyes. This enzyme is considered to have a critical role in governing the quality and economics of fruits and vegetables, as tyrosinase activity can lead to spoilage through browning. Development of tyrosinase inhibitors is a promising approach to combat hyperpigmentation conditions like ephelides, lentigo, freckles and post-inflammatory hyperpigmentation. In the present study, we have used a docking algorithm to simulate binding between tyrosinase and hydroxy-substituted naphthyl chalcone oxime compounds and studied the inhibition of tyrosinase. The results of virtual screening studies indicated that the estimated free energy of binding of all the docked ligands ranged between -19.29 and -9.12 kcal/mol. Two of the oximes synthesized were identified as competitive tyrosinase inhibitors and were found to be twice as potent as the control kojic acid with their IC50 values of 12.22 mu M and 19.45 mu M, respectively. This strategy of integrating experimental and virtual screening methods could give better insights to explore potent depigmentation agents. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.08.033

文献信息

• Integrated kinetic studies and computational analysis on naphthyl chalcones as mushroom tyrosinase inhibitors
  作者：Sini Radhakrishnan、Ronald Shimmon、Costa Conn、Anthony Baker

  DOI：10.1016/j.bmcl.2015.08.033

  日期：2015.10

  Melanin helps to protect skin from the damaging ultraviolet radiation of the sun. Tyrosinase, the key enzyme in melanogenesis is responsible for coloration of skin, hair and eyes. This enzyme is considered to have a critical role in governing the quality and economics of fruits and vegetables, as tyrosinase activity can lead to spoilage through browning. Development of tyrosinase inhibitors is a promising approach to combat hyperpigmentation conditions like ephelides, lentigo, freckles and post-inflammatory hyperpigmentation. In the present study, we have used a docking algorithm to simulate binding between tyrosinase and hydroxy-substituted naphthyl chalcone oxime compounds and studied the inhibition of tyrosinase. The results of virtual screening studies indicated that the estimated free energy of binding of all the docked ligands ranged between -19.29 and -9.12 kcal/mol. Two of the oximes synthesized were identified as competitive tyrosinase inhibitors and were found to be twice as potent as the control kojic acid with their IC50 values of 12.22 mu M and 19.45 mu M, respectively. This strategy of integrating experimental and virtual screening methods could give better insights to explore potent depigmentation agents. (C) 2015 Elsevier Ltd. All rights reserved.
• Development of hydroxylated naphthylchalcones as polyphenol oxidase inhibitors: Synthesis, biochemistry and molecular docking studies
  作者：Sini Radhakrishnan、Ronald Shimmon、Costa Conn、Anthony Baker

  DOI：10.1016/j.bioorg.2015.10.003

  日期：2015.12

  Polyphenol oxidase (Tyrosinase) has received great attention, since it is the key enzyme in melanin biosynthesis. In this study, novel hydroxy naphthylchalcone compounds were synthesized, and their inhibitory effects on mushroom tyrosinase activity were evaluated. The structures of the compounds synthesized were confirmed by H-1 NMR, C-13 NMR, FTIR and HRMS. Two of the compounds synthesized inhibited the diphenolase activity of tyrosinase in a dose dependent manner and exhibited much higher tyrosinase inhibitory activities (IC50 values of 10.4 mu M and 14.4 mu M, respectively) than the positive control, kojic acid (IC50: 27.5 mu M). Kinetic analysis showed that their inhibition was reversible. Both the novel compounds displayed competitive inhibition with their K-i values of 3.8 mu M and 4.5 mu M, respectively. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues. This study suggests hydroxy naphthylchalcone compounds to serve as promising candidates for use as depigmentation agents. (C) 2015 Elsevier Inc. All rights reserved.