tert-butyl N-[3-[benzyl-[4-[(1,4-dioxonaphthalen-2-yl)amino]butyl]amino]propyl]carbamate | 1001379-65-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl N-[3-[benzyl-[4-[(1,4-dioxonaphthalen-2-yl)amino]butyl]amino]propyl]carbamate
• CAS: 1001379-65-2
• 化学式: C₂₉H₃₇N₃O₄
• 分子量: 491.63
• InChiKey: LFCQPNHDNGWPJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  14
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  87.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl N-[3-[benzyl-[4-[(1,4-dioxonaphthalen-2-yl)amino]butyl]amino]propyl]carbamate 在 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.17h， 以99%的产率得到2-[4-[3-Aminopropyl(benzyl)amino]butylamino]naphthalene-1,4-dione
  参考文献：
  名称：

  与多胺结合可增强萘醌对人胶质母细胞瘤细胞的抗肿瘤活性。

  摘要：

  胶质母细胞瘤（GBM）是最常见和最具破坏性的原发性脑肿瘤，被认为是最致命的人类癌症。在这种情况下，已经进行了广泛的努力来开发对GBM表现出抗增殖和抗转移作用的新药。在能够抑制与癌症相关的重要生物学靶标的化合物中发现了1,4-萘醌（1,4-NQ）支架，包括DNA拓扑异构酶，Hsp90和单胺氧化酶。潜在的抗肿瘤药1,4-NQs是植物来源的拉帕胆酚（2-羟基-3-异戊烯基-1,4-萘醌），被发现具有抗Walker-256癌和吉田肉瘤的活性。在本研究中，我们研究了多巴胺，去甲拉帕考和Lawone的多胺（PA）偶联衍生物对人GBM细胞生长和侵袭的影响。与PA（亚精胺类似物）的结合导致1,4-NQs细胞毒性的剂量依赖性和时间依赖性增加。另外，PA结合后增加了拉帕胆酚对GBM细胞入侵的体外抑制作用。先前的生化实验表明，这些PA-1,4-NQs能够抑制DNA人拓扑异构酶II-α（topo2α），这是一种参

  DOI：

  10.1097/cad.0000000000000619

文献信息

• Beyond Topoisomerase Inhibition: Antitumor 1,4-Naphthoquinones as Potential Inhibitors of Human Monoamine Oxidase
  作者：Eduardo Coelho-Cerqueira、Paulo A. Netz、Vanessa P. do Canto、Angelo C. Pinto、Cristian Follmer

  DOI：10.1111/cbdd.12255

  日期：2014.4

  Monoamine oxidase (MAO) action has been involved in the regulation of neurotransmitters levels, cell signaling, cellular growth, and differentiation as well as in the balance of the intracellular polyamine levels. Although so far obscure, MAO inhibitors are believed to have some effect on tumors progression. 1,4‐naphthoquinone (1,4‐NQ) has been pointed out as a potential pharmacophore for inhibition of both MAO and DNA topoisomerase activities, this latter associated with antitumor activity. Herein, we demonstrated that certain antitumor 1,4‐NQs, including spermidine‐1,4‐NQ, lapachol, and nor‐lapachol display inhibitory activity on human MAO‐A and MAO‐B. Kinetic studies indicated that these compounds are reversible and competitive MAO inhibitors, being the enzyme selectivity greatly affected by substitutions on 1,4‐NQ ring. Molecular docking studies suggested that the most potent MAO inhibitors are capable to bind to the MAO active site in close proximity of flavin moiety. Furthermore, ability to inhibit both MAO‐A and MAO‐B can be potentialized by the formation of hydrogen bonds between these compounds and FAD and/or the residues in the active site. Although spermidine‐1,4‐NQs exhibit antitumor action primarily by inhibiting topoisomerase via DNA intercalation, our findings suggest that their effect on MAO activity should be taken into account when their application in cancer therapy is considered.