3-(4-羟基亚苄基)吲哚-2-酮 | 293302-14-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 3-(4-羟基亚苄基)吲哚-2-酮
• 英文名称: 3-(4-hydroxybenzylidene)indolin-2-one
• 英文别名: 3-[(4-hydroxyphenyl)methylidene]-1H-indol-2-one
• CAS: 293302-14-4
• 化学式: C₁₅H₁₁NO₂
• 分子量: 237.258
• InChiKey: PLAOAGFXNCEZMZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-二甲氧基苯甲酰氯 、 3-(4-羟基亚苄基)吲哚-2-酮 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以42%的产率得到4-((2-oxoindolin-3-ylidene)methyl)phenyl 3,4-dimethoxybenzoate
  参考文献：
  名称：

  In silico designing of domain B selective gyrase inhibitors for effective treatment of resistant tuberculosis

  摘要：

  One of the major mechanisms followed by the therapeutic agents to target the causative organism of TB, Mycobacterium tuberculosis, involves disruption of its DNA replication cycle. The process of replication involves two steps, i.e., breakage and reunion of DNA at gyrase A (GyrA) domain and ATP hydrolysis at gyrase B (GyrB) domain, both occur simultaneously. Current therapy for multi-drug resistant TB (MDR-TB) involves FDA approved, fluoroquinolone-based antibiotics, which act by targeting replication process at GyrA domain. However, resistance against fluoroquinolones due to mutations in the GyrA domain has limited the use of this therapy and shifted the focus of research community on GyrB domain. Thus, in the present study novel chemotherapeutic agents for resistant TB were designed by exploring GyrB domain using in silico techniques. Pharmacophore model of GyrB domain was employed for screening an In-house database. Followed by cross-screening via a qualitative Hip-Hop pharmacophore model for GyrA to remove non-selective gyrase B inhibitors. Further molecular dynamics simulations and MM-GBSA calculations were performed to determine stability and binding affinity of the screened molecules. These analyses resulted in five putative oxindole based selective GyrB domain inhibitors, which were synthesized and evaluated for anti-tubercular activity against M. tuberculosis H(37)Rv strain. Two compounds exhibited significant anti-TB activity, whereas other three compounds were found to be outliers of the in silico study.

  DOI：

  10.1016/j.tube.2018.08.005
• 作为产物：
  描述：

  2-吲哚酮 、 对羟基苯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 3-(4-羟基亚苄基)吲哚-2-酮
  参考文献：
  名称：

  In silico designing of domain B selective gyrase inhibitors for effective treatment of resistant tuberculosis

  摘要：

  One of the major mechanisms followed by the therapeutic agents to target the causative organism of TB, Mycobacterium tuberculosis, involves disruption of its DNA replication cycle. The process of replication involves two steps, i.e., breakage and reunion of DNA at gyrase A (GyrA) domain and ATP hydrolysis at gyrase B (GyrB) domain, both occur simultaneously. Current therapy for multi-drug resistant TB (MDR-TB) involves FDA approved, fluoroquinolone-based antibiotics, which act by targeting replication process at GyrA domain. However, resistance against fluoroquinolones due to mutations in the GyrA domain has limited the use of this therapy and shifted the focus of research community on GyrB domain. Thus, in the present study novel chemotherapeutic agents for resistant TB were designed by exploring GyrB domain using in silico techniques. Pharmacophore model of GyrB domain was employed for screening an In-house database. Followed by cross-screening via a qualitative Hip-Hop pharmacophore model for GyrA to remove non-selective gyrase B inhibitors. Further molecular dynamics simulations and MM-GBSA calculations were performed to determine stability and binding affinity of the screened molecules. These analyses resulted in five putative oxindole based selective GyrB domain inhibitors, which were synthesized and evaluated for anti-tubercular activity against M. tuberculosis H(37)Rv strain. Two compounds exhibited significant anti-TB activity, whereas other three compounds were found to be outliers of the in silico study.

  DOI：

  10.1016/j.tube.2018.08.005