N'-(3,4,5-trimethoxybenzoyl)naphthalene-1-carbohydrazide

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: N'-(3,4,5-trimethoxybenzoyl)naphthalene-1-carbohydrazide
• 化学式: C₂₁H₂₀N₂O₅
• 分子量: 380.4
• InChiKey: SQUQJQRCAVRHSN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  85.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酸甲酯 在 吡啶 、 一水合肼 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 2.5h， 生成 N'-(3,4,5-trimethoxybenzoyl)naphthalene-1-carbohydrazide
  参考文献：
  名称：

  N-(1′-naphthyl)-3,4,5-trimethoxybenzohydrazide as microtubule destabilizer: Synthesis, cytotoxicity, inhibition of cell migration and in vivo activity against acute lymphoblastic leukemia

  摘要：

  Tubulin-interacting agents, like vinca alkaloid and taxanes, play a fundamental role in cancer chemotherapy, making cellular microtubules (MT), one of the few validated anticancer targets. Cancer resistance to classical MT inhibitors has motivated the development of novel molecules with increased efficacy and lower toxicity. Aiming at designing structurally-simple inhibitors of MT assembly, we synthesized a series of thirty-one 3,4,5-trimethoxy-hydrazones and twenty-five derivatives or analogs. Docking simulations suggested that a representative N-acylhydrazone could adopt an appropriate stereochemistry inside the colchicine-binding domain of tubulin. Several of these compounds showed anti-leukemia effects in the nanomolar concentration range. Interference with MT polymerization was validated by the compounds' ability to inhibit MT assembly at the biochemical and cellular level. Selective toxicity investigations done with the most potent compound, a 3,4,5-trimethoxy-hydrazone with a 1-naphthyl group, showed remarkably selective toxicity against leukemia cells in comparison with stimulated normal lymphocytes, and no acute toxicity in vivo. Finally, this molecule was as active as vincristine in a murine model of human acute lymphoblastic leukemia at a weekly dose of 1 mg/kg. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.02.041

文献信息

• N-(1′-naphthyl)-3,4,5-trimethoxybenzohydrazide as microtubule destabilizer: Synthesis, cytotoxicity, inhibition of cell migration and in vivo activity against acute lymphoblastic leukemia
  作者：Lívia B. Salum、Alessandra Mascarello、Rafael R. Canevarolo、Wanessa F. Altei、Angelo B.A. Laranjeira、Patrícia D. Neuenfeldt、Taisa R. Stumpf、Louise D. Chiaradia-Delatorre、Laura L. Vollmer、Hikmat N. Daghestani、Carolina P. de Souza Melo、André B. Silveira、Paulo C. Leal、Marisa J.S. Frederico、Leandro F. do Nascimento、Adair R.S. Santos、Adriano D. Andricopulo、Billy W. Day、Rosendo A. Yunes、Andreas Vogt、José A. Yunes、Ricardo J. Nunes

  DOI：10.1016/j.ejmech.2015.02.041

  日期：2015.5

  Tubulin-interacting agents, like vinca alkaloid and taxanes, play a fundamental role in cancer chemotherapy, making cellular microtubules (MT), one of the few validated anticancer targets. Cancer resistance to classical MT inhibitors has motivated the development of novel molecules with increased efficacy and lower toxicity. Aiming at designing structurally-simple inhibitors of MT assembly, we synthesized a series of thirty-one 3,4,5-trimethoxy-hydrazones and twenty-five derivatives or analogs. Docking simulations suggested that a representative N-acylhydrazone could adopt an appropriate stereochemistry inside the colchicine-binding domain of tubulin. Several of these compounds showed anti-leukemia effects in the nanomolar concentration range. Interference with MT polymerization was validated by the compounds' ability to inhibit MT assembly at the biochemical and cellular level. Selective toxicity investigations done with the most potent compound, a 3,4,5-trimethoxy-hydrazone with a 1-naphthyl group, showed remarkably selective toxicity against leukemia cells in comparison with stimulated normal lymphocytes, and no acute toxicity in vivo. Finally, this molecule was as active as vincristine in a murine model of human acute lymphoblastic leukemia at a weekly dose of 1 mg/kg. (C) 2015 Elsevier Masson SAS. All rights reserved.