N'-(3,5-di-tert-butyl-4-oxocyclohexa-2,5-dienylidene)isonicotinohydrazide

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: N'-(3,5-di-tert-butyl-4-oxocyclohexa-2,5-dienylidene)isonicotinohydrazide
• 英文别名: N-[(3,5-ditert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)amino]pyridine-4-carboxamide
• 化学式: C₂₀H₂₅N₃O₂
• 分子量: 339.437
• InChiKey: HCSMEIDSTDGNNY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  71.42
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  异烟肼 、 2,6-二叔丁基苯醌 以 氯仿 为溶剂， 反应 48.0h， 以45%的产率得到N'-(3,5-di-tert-butyl-4-oxocyclohexa-2,5-dienylidene)isonicotinohydrazide
  参考文献：
  名称：

  Synthesis of NG-061 and Its Analogs, and Their Biological Evaluation as an Enhancer of Nerve Growth Factor.

  摘要：

  一种新型神经生长因子（NGF）增强剂NG-061，已从青霉菌（Penicillium minioluteum F-4627）的发酵液中分离，采用单一步骤合成自甲氧基苯醌和苯乙酰肼。同时，还合成了一系列酰肼衍生物，并通过对大鼠嗜铬细胞瘤细胞系PC12的评价，测试了它们对NGF在神经突生长中的神经营养效应的增强活性。

  DOI：

  10.1248/cpb.48.1470

文献信息

• Synthesis of NG-061 and Its Analogs, and Their Biological Evaluation as an Enhancer of Nerve Growth Factor.
  作者：Tadashi EGUCHI、Shinobu KANAI、Katsumi KAKINUMA、Tadayasu OKAZAKI、Kazutoshi MIZOUE

  DOI：10.1248/cpb.48.1470

  日期：——

  A novel potentiator of nerve growth factor (NGF), NG-061, which had been isolated from the fermentation broth of Penicillium minioluteum F-4627, was synthesized from methoxybenzoquinone and phenylacetylhydrazine in a single step. Aseries of acyl hydrazone derivatives were also synthesized and their potentiator activity of neurotrophic effect of NGF on neurite outgrowth was evaluated by assay with a rat pheochromocytoma cell line PC12.

  一种新型神经生长因子（NGF）增强剂NG-061，已从青霉菌（Penicillium minioluteum F-4627）的发酵液中分离，采用单一步骤合成自甲氧基苯醌和苯乙酰肼。同时，还合成了一系列酰肼衍生物，并通过对大鼠嗜铬细胞瘤细胞系PC12的评价，测试了它们对NGF在神经突生长中的神经营养效应的增强活性。
• Novel dual cyclooxygenase and lipoxygenase inhibitors targeting hyaluronan–CD44v6 pathway and inducing cytotoxicity in colon cancer cells
  作者：Suniti Misra、Shibnath Ghatak、Neha Patil、Prasad Dandawate、Vinita Ambike、Shreelekha Adsule、Deepak Unni、K. Venkateswara Swamy、Subhash Padhye

  DOI：10.1016/j.bmc.2013.02.033

  日期：2013.5

  Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) enzyme have been found to play a role in promoting growth in colon cancer cell lines. The di-tert-butyl phenol class of compounds has been found to inhibit both COX-2 and 5-LOX enzymes with proven effectiveness in arresting tumor growth. In the present study, the structural analogs of 2,6 di-tert-butyl-p-benzoquinone (BQ) appended with hydrazide side chain were found to inhibit COX-2 and 5-LOX enzymes at micromolar concentrations. Molecular docking of the compounds into COX-2 and 5-LOX protein cavities indicated strong binding interactions supporting the observed cytototoxicities. The signaling interaction between endogenous hyaluronan and CD44 has been shown to regulate COX-2 activities through ErbB2 receptor tyrosine kinase (RTK) activation. In the present studies it has been observed for the first time, that three of our COX/5-LOX dual inhibitors inhibit proliferation upon hydrazide substitution and prevent the activity of pro-angiogenic factors in HCA-7, HT-29, Apc10.1 cells as well as the hyaluronan synthase-2 (Has2) enzyme over-expressed in colon cancer cells, through inhibition of the hyaluronan/CD44v6 cell survival pathway. Since there is a substantial enhancement in the antiproliferative activities of these compounds upon hydrazide substitution, the present work opens up new opportunities for evolving novel active compounds of BQ series for inhibiting colon cancer. (C) 2013 Elsevier Ltd. All rights reserved.