2-hydroxy-3-(1-methyl-allyl)-[1,4]naphthoquinone | 52422-69-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 2-hydroxy-3-(1-methyl-allyl)-[1,4]naphthoquinone
• 英文别名: 2-Hydroxy-3-(1-methyl-allyl)-[1,4]naphthochinon；3-(Methylallyl)-2-hydroxy-1,4-naphthoquinone
• CAS: 52422-69-2
• 化学式: C₁₄H₁₂O₃
• 分子量: 228.247
• InChiKey: VDCFHJCYBRKTAG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  54.37
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  2-hydroxy-3-(1-methyl-allyl)-[1,4]naphthoquinone 在 五氯化铌 作用下， 以 二氯甲烷 为溶剂， 生成 2,3-dihydro-2,3-dimethylnaphthol[1,2-b]furan-4,5-dione
  参考文献：
  名称：

  Synthesis and evaluation of (±)-dunnione and its ortho-quinone analogues as substrates for NAD(P)H:quinone oxidoreductase 1 (NQO1)

  摘要：

  Natural product (+/-)-dunnione (2) and its ortho-quinone analogues (3-8) were synthesized and found to be substrates for NQO1. The structure-activity relationship study revealed that the biological activity was favored by the presence of methyl group at the C ring and methoxy group at the A ring. The docking studies supported the rationalization of the metabolic studies. Deeper location in the active site of NQO1, interactions with hydrophobic pocket and C-H center dot center dot center dot pi interactions with the adjacent Phe178 residue contributed to the better catalytic efficiency and specificity to NQO1. Cytotoxicity studies and determination of superoxide (O-2(center dot)) production in the presence and absence of the NOQ1 inhibitor dicoumarol confirmed that the ortho-quinones exerted their antitumor activity through NQO1-mediated ROS production by redox cycling. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2015.01.057
• 作为产物：
  描述：

  2-羟基-1,4-萘醌 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 2-hydroxy-3-(1-methyl-allyl)-[1,4]naphthoquinone
  参考文献：
  名称：

  Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile

  摘要：

  In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b] furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control beta-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H... pi interactions with Trp105 and Phe178 residues compared to the control beta-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation. (C) 2017 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2017.02.004

文献信息

• WO2008/66299
  申请人：——

  公开号：——

  公开（公告）日：——
• WO2008/66297
  申请人：——

  公开号：——

  公开（公告）日：——
• THE ALKYLATION OF HYDROXYNAPHTHOQUINONE. III. A SYNTHESIS OF LAPACHOL
  作者：Louis F. Fieser

  DOI：10.1021/ja01402a030

  日期：1927.3
• NOVEL ORTHO-NAPHTHOQUINONE DERIVATIVES, NOVEL SYNTHESIS THEREFOR, AND THEIR USE IN THE INHIBITION OF NEOPLASTIC CELL GROWTH
  申请人：WISCONSIN ALUMNI RESEARCH FOUNDATION

  公开号：EP0888326A2

  公开（公告）日：1999-01-07
• US5824700A
  申请人：——

  公开号：US5824700A

  公开（公告）日：1998-10-20