genistin-ethylidene-lomefloxacin | 1613083-70-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: genistin-ethylidene-lomefloxacin
• 英文别名: 1-Ethyl-6,8-difluoro-7-[4-[2-[5-hydroxy-3-(4-hydroxyphenyl)-4-oxo-chromen-7-yl]oxyethyl]-3-methyl-piperazin-1-yl]-4-oxo-quinoline-3-carboxylic acid；1-ethyl-6,8-difluoro-7-[4-[2-[5-hydroxy-3-(4-hydroxyphenyl)-4-oxochromen-7-yl]oxyethyl]-3-methylpiperazin-1-yl]-4-oxoquinoline-3-carboxylic acid
• CAS: 1613083-70-7
• 化学式: C₃₄H₃₁F₂N₃O₈
• 分子量: 647.632
• InChiKey: YGJKGPHFVHAGRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  47
• 可旋转键数：
  8
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  140
• 氢给体数：
  3
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  染料木素 在 4-二甲氨基吡啶 、 potassium carbonate 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 生成 genistin-ethylidene-lomefloxacin
  参考文献：
  名称：

  Design, synthesis, and evaluation of novel fluoroquinolone–flavonoid hybrids as potent antibiotics against drug-resistant microorganisms

  摘要：

  Based on a rationally conceived pharmacophore model to build a multi-target bacterial topoisomerase inhibitor, twenty-one fluoroquinolone-flavonoid hybrids were synthesized. Some obtained hybrids show excellent antibacterial activity against drug-resistant microorganisms with narigenin-ciprofloxacin being the most active, showing 8, 43, 23 and 88 times better activity than ciprofloxacin against Escherichia coli ATCC 35218, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 90873, respectively. Drug accumulation and DNA supercoiling assays of two active analogues revealed potent inhibition of both the DNA gyrase and efflux pump, confirming the desired dual mode of action. Molecular docking study disclosed that the introduced flavonoid moiety not only provides several additional interactions but also does not disturb the binding mode of the floxacin moiety. Our data also demonstrated that development of antifungals is possible from fluoroquinolones modified at C-7 position.

  DOI：

  10.1016/j.ejmech.2014.04.037

文献信息

• Design, synthesis, and evaluation of novel fluoroquinolone–flavonoid hybrids as potent antibiotics against drug-resistant microorganisms
  作者：Zhu-Ping Xiao、Xu-Dong Wang、Peng-Fei Wang、Yin Zhou、Jing-Wen Zhang、Lei Zhang、Jiao Zhou、Sha-Sha Zhou、Hui Ouyang、Xiao-Yi Lin、Manzira Mustapa、Asaimuguli Reyinbaike、Hai-Liang Zhu

  DOI：10.1016/j.ejmech.2014.04.037

  日期：2014.6

  Based on a rationally conceived pharmacophore model to build a multi-target bacterial topoisomerase inhibitor, twenty-one fluoroquinolone-flavonoid hybrids were synthesized. Some obtained hybrids show excellent antibacterial activity against drug-resistant microorganisms with narigenin-ciprofloxacin being the most active, showing 8, 43, 23 and 88 times better activity than ciprofloxacin against Escherichia coli ATCC 35218, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 25923 and Candida albicans ATCC 90873, respectively. Drug accumulation and DNA supercoiling assays of two active analogues revealed potent inhibition of both the DNA gyrase and efflux pump, confirming the desired dual mode of action. Molecular docking study disclosed that the introduced flavonoid moiety not only provides several additional interactions but also does not disturb the binding mode of the floxacin moiety. Our data also demonstrated that development of antifungals is possible from fluoroquinolones modified at C-7 position.