12-bromododecyl 2,4-dihydroxybenzoate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 12-bromododecyl 2,4-dihydroxybenzoate
• 英文别名: 12-Bromododecyl 2,4-dihydroxybenzoate
• 化学式: C₁₉H₂₉BrO₄
• 分子量: 401.341
• InChiKey: ZWXMIKYFHIDBCH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.5
• 重原子数：
  24
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  喹啉 、 12-bromododecyl 2,4-dihydroxybenzoate 以 乙腈 为溶剂， 反应 39.0h， 以29%的产率得到1-(12-((2,4-dihydroxybenzoyl)oxy)dodecyl)quinolin-1-ium bromide
  参考文献：
  名称：

  Conjugates of 2,4-Dihydroxybenzoate and Salicylhydroxamate and Lipocations Display Potent Antiparasite Effects by Efficiently Targeting the Trypanosoma brucei and Trypanosoma congolense Mitochondrion

  摘要：

  We investigated a chemical strategy to boost the trypanocidal activity of 2,4-dihydroxybenzoic acid (2,4-DHBA)- and salicylhydroxamic acid (SHAM)-based trypanocides with triphenylphosphonium and quinolinium lipophilic cations (LC). Three series of LC conjugates were synthesized that were active in the submicromolar (5a-d and 10d-f to low nanomolar (6a-f) range against wild-type and multidrug resistant strains of African trypanosomes (Trypanosoma brucei brucei and T. congolense). This represented an improvement in trypanocidal potency of at least 200-fold, and up to >10 000-fold, compared with that of non-LC-coupled parent compounds 2,4-DHBA and SHAM. Selectivity over human cells was >500 and reached >23 000 for 6e. Mechanistic studies showed that 6e did not inhibit the cell cycle but affected parasite respiration in a dose-dependent manner. Inhibition of trypanosome alternative oxidase and the mitochondrial membrane potential was also studied for selected compounds. We conclude that effective mitochondrial targeting greatly potentiated the activity of these series of compounds.

  DOI：

  10.1021/acs.jmedchem.6b01740
• 作为产物：
  描述：

  1,12-二溴十二烷 、 2,4-二羟基苯甲酸 、 N,N-二甲基甲酰胺 在 碳酸氢钠 作用下， 以48%的产率得到12-bromododecyl 2,4-dihydroxybenzoate
  参考文献：
  名称：

  Conjugates of 2,4-Dihydroxybenzoate and Salicylhydroxamate and Lipocations Display Potent Antiparasite Effects by Efficiently Targeting the Trypanosoma brucei and Trypanosoma congolense Mitochondrion

  摘要：

  We investigated a chemical strategy to boost the trypanocidal activity of 2,4-dihydroxybenzoic acid (2,4-DHBA)- and salicylhydroxamic acid (SHAM)-based trypanocides with triphenylphosphonium and quinolinium lipophilic cations (LC). Three series of LC conjugates were synthesized that were active in the submicromolar (5a-d and 10d-f to low nanomolar (6a-f) range against wild-type and multidrug resistant strains of African trypanosomes (Trypanosoma brucei brucei and T. congolense). This represented an improvement in trypanocidal potency of at least 200-fold, and up to >10 000-fold, compared with that of non-LC-coupled parent compounds 2,4-DHBA and SHAM. Selectivity over human cells was >500 and reached >23 000 for 6e. Mechanistic studies showed that 6e did not inhibit the cell cycle but affected parasite respiration in a dose-dependent manner. Inhibition of trypanosome alternative oxidase and the mitochondrial membrane potential was also studied for selected compounds. We conclude that effective mitochondrial targeting greatly potentiated the activity of these series of compounds.

  DOI：

  10.1021/acs.jmedchem.6b01740

文献信息

• Conjugates of 2,4-Dihydroxybenzoate and Salicylhydroxamate and Lipocations Display Potent Antiparasite Effects by Efficiently Targeting the <i>Trypanosoma brucei</i> and <i>Trypanosoma congolense</i> Mitochondrion
  作者：Francisco José Fueyo González、Godwin U. Ebiloma、Carolina Izquierdo García、Victor Bruggeman、José María Sánchez Villamañán、Anne Donachie、Emmanuel Oluwadare Balogun、Daniel Ken Inaoka、Tomoo Shiba、Shigeharu Harada、Kiyoshi Kita、Harry P. de Koning、Christophe Dardonville

  DOI：10.1021/acs.jmedchem.6b01740

  日期：2017.2.23

  We investigated a chemical strategy to boost the trypanocidal activity of 2,4-dihydroxybenzoic acid (2,4-DHBA)- and salicylhydroxamic acid (SHAM)-based trypanocides with triphenylphosphonium and quinolinium lipophilic cations (LC). Three series of LC conjugates were synthesized that were active in the submicromolar (5a-d and 10d-f to low nanomolar (6a-f) range against wild-type and multidrug resistant strains of African trypanosomes (Trypanosoma brucei brucei and T. congolense). This represented an improvement in trypanocidal potency of at least 200-fold, and up to >10 000-fold, compared with that of non-LC-coupled parent compounds 2,4-DHBA and SHAM. Selectivity over human cells was >500 and reached >23 000 for 6e. Mechanistic studies showed that 6e did not inhibit the cell cycle but affected parasite respiration in a dose-dependent manner. Inhibition of trypanosome alternative oxidase and the mitochondrial membrane potential was also studied for selected compounds. We conclude that effective mitochondrial targeting greatly potentiated the activity of these series of compounds.