1-benzyl-5-chloro-2-(thiophen-2-yl)-1H-benzo[d]imidazole

• 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: 1-benzyl-5-chloro-2-(thiophen-2-yl)-1H-benzo[d]imidazole
• 英文别名: 1-Benzyl-5-chloro-2-thiophen-2-ylbenzimidazole
• 化学式: C₁₈H₁₃ClN₂S
• 分子量: 324.834
• InChiKey: ARALWJZPJBBGJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  46.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  N-苄基-4-氯-2-硝基苯胺 在 sodium metabisulfite 、 tin(II) chloride dihdyrate 作用下， 以 乙醇 、 水 为溶剂， 反应 7.0h， 生成 1-benzyl-5-chloro-2-(thiophen-2-yl)-1H-benzo[d]imidazole
  参考文献：
  名称：

  Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents

  摘要：

  In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo [d] imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent with an IC50, of 7.01 +/- 0.20 mu M and arresting MCF-7 cell growth at G2/M phase and S phase. Induction of apoptosis was confirmed by morphological changes like cell shrinkage, blebbing and cell wall deformation, dose dependent increase in the mitochondrial membrane potential (Delta Psi m) and ROS levels. Further, dose dependent decrease in Gal-1 protein levels proves Gal-1 mediated apoptosis by 6g. Molecular docking studies were performed to understand the Gal-1 interaction with compound 6g. In addition, RP-HPLC studies showed 85.44% of 6g binding to Gal-1. Binding affinity studies by fluorescence spectroscopy and Surface Plasmon Resonance (SPR) showed that 6g binds to Gal-1 with binding constant (K-a) of 1.2 x 10(4) M-1 and equilibrium constant K-D value of 5.76 x 10(-4) M respectively.

  DOI：

  10.1016/j.bioorg.2019.103016

文献信息

• Synthesis of 1-benzyl-1H-benzimidazoles as galectin-1 mediated anticancer agents
  作者：Nerella Sridhar Goud、S. Mahammad Ghouse、Jatoth Vishnu、D. Komal、Venu Talla、Ravi Alvala、Jakkula Pranay、Janish Kumar、Insaf A. Qureshi、Mallika Alvala

  DOI：10.1016/j.bioorg.2019.103016

  日期：2019.8

  In our pursuit to develop novel non-carbohydrate small molecule Galectin-1 Inhibitors, we have designed a series of 1-benzyl-1H-benzimidazole derivatives and demonstrated their anticancer activity. The compound 6g, 4-(1-benzyl-5-chloro-1H-benzo [d] imidazol-2-yl)-N-(4-hydroxyphenyl) benzamide was found to be most potent with an IC50, of 7.01 +/- 0.20 mu M and arresting MCF-7 cell growth at G2/M phase and S phase. Induction of apoptosis was confirmed by morphological changes like cell shrinkage, blebbing and cell wall deformation, dose dependent increase in the mitochondrial membrane potential (Delta Psi m) and ROS levels. Further, dose dependent decrease in Gal-1 protein levels proves Gal-1 mediated apoptosis by 6g. Molecular docking studies were performed to understand the Gal-1 interaction with compound 6g. In addition, RP-HPLC studies showed 85.44% of 6g binding to Gal-1. Binding affinity studies by fluorescence spectroscopy and Surface Plasmon Resonance (SPR) showed that 6g binds to Gal-1 with binding constant (K-a) of 1.2 x 10(4) M-1 and equilibrium constant K-D value of 5.76 x 10(-4) M respectively.