2-methyl-N'-[(E)-(2,3,4-trimethoxyphenyl)methylidene]-1H-benzimidazole-5-carbohydrazide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并咪唑类
• 英文名称: 2-methyl-N'-[(E)-(2,3,4-trimethoxyphenyl)methylidene]-1H-benzimidazole-5-carbohydrazide
• 英文别名: 2-methyl-N-[(E)-(2,3,4-trimethoxyphenyl)methylideneamino]-3H-benzimidazole-5-carboxamide
• 化学式: C₁₉H₂₀N₄O₄
• 分子量: 368.392
• InChiKey: ZYGSGRRNMIWNRP-KEBDBYFISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  97.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2-甲基-3H-苯并咪唑-5-羧酸 在 溶剂黄146 、 N,N'-羰基二咪唑 、 三氟乙酸 作用下， 以 二氯甲烷 、 异丙醇 、 乙腈 为溶剂， 反应 29.0h， 生成 2-methyl-N'-[(E)-(2,3,4-trimethoxyphenyl)methylidene]-1H-benzimidazole-5-carbohydrazide
  参考文献：
  名称：

  Synthesis and biological evaluation of 2-methyl-1H-benzimidazole-5-carbohydrazides derivatives as modifiers of redox homeostasis of Trypanosoma cruzi

  摘要：

  Twelve novel benzimidazole derivatives were synthesized and their in vitro activities against epimastigotes of Trypanosoma cruzi were evaluated. Two derivatives (6 and 7), which have 4-hydroxy-3-methoxyphenyl moiety in their structures, proved to be the most active in inhibiting the parasite growth. Compound 6 showed a trypanocidal activity higher than benznidazole (IC50 = 5 mu M and 7.5 mu M, respectively) and less than nifurtimox (IC50 = 3.6 mu M). In addition, the ability of 6 and 7 to modify the redox homeostasis in T cruzi epimastigote was studied; cysteine and glutathione increased in parasites exposed to both compounds, whereas trypanothione only increased with 7 treatment. These results suggest that the decrease in viability of T. cruzi may be attributed to the change in cellular redox balance caused by compound 6 or 7. Furthermore, compounds 6 and 7 showed CC50 values of 160.64 and 160.66 mu M when tested in mouse macrophage cell line J774 and selectivity indexes (macrophage/parasite) of 32 and 20.1, respectively. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2017.06.013

文献信息

• Synthesis and biological evaluation of 2-methyl-1H-benzimidazole-5-carbohydrazides derivatives as modifiers of redox homeostasis of Trypanosoma cruzi
  作者：Silvia Melchor-Doncel de la Torre、Citlali Vázquez、Zabdi González-Chávez、Lilián Yépez-Mulia、Rocío Nieto-Meneses、Ricardo Jasso-Chávez、Emma Saavedra、Francisco Hernández-Luis

  DOI：10.1016/j.bmcl.2017.06.013

  日期：2017.8

  Twelve novel benzimidazole derivatives were synthesized and their in vitro activities against epimastigotes of Trypanosoma cruzi were evaluated. Two derivatives (6 and 7), which have 4-hydroxy-3-methoxyphenyl moiety in their structures, proved to be the most active in inhibiting the parasite growth. Compound 6 showed a trypanocidal activity higher than benznidazole (IC50 = 5 mu M and 7.5 mu M, respectively) and less than nifurtimox (IC50 = 3.6 mu M). In addition, the ability of 6 and 7 to modify the redox homeostasis in T cruzi epimastigote was studied; cysteine and glutathione increased in parasites exposed to both compounds, whereas trypanothione only increased with 7 treatment. These results suggest that the decrease in viability of T. cruzi may be attributed to the change in cellular redox balance caused by compound 6 or 7. Furthermore, compounds 6 and 7 showed CC50 values of 160.64 and 160.66 mu M when tested in mouse macrophage cell line J774 and selectivity indexes (macrophage/parasite) of 32 and 20.1, respectively. (C) 2017 Elsevier Ltd. All rights reserved.