desferrioxamine | 1381849-20-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: desferrioxamine
• 英文别名: 7-{4-[4-(5-{N-4-[5-(N-4-{5-[N-acetyl-(hydroxyamino)]pentylamino}-4-oxobutyryl(hydroxyamino))pentylamino]-4-oxobutyryl(hydroxyamino)}pentylamino)-4-oxobutyryl]-1-piperazinyl}-1-cyclopropyl-6-fluoro-4-oxo-1H-quinoline-3-carboxylic acid；7-[4-[4-[5-[[4-[5-[[4-[5-[Acetyl(hydroxy)amino]pentylamino]-4-oxobutanoyl]-hydroxyamino]pentylamino]-4-oxobutanoyl]-hydroxyamino]pentylamino]-4-oxobutanoyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 1381849-20-2
• 化学式: C₄₆H₆₈FN₉O₁₃
• 分子量: 974.097
• InChiKey: KROPLJHNEUEACH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  69
• 可旋转键数：
  30
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  290
• 氢给体数：
  7
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  iron(III) chloride 、 desferrioxamine 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以84%的产率得到
  参考文献：
  名称：

  Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency

  摘要：

  Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using small-molecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 mu M in Escherichia con, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 mu M), Staphylococcus aureus (0.94 mu M), and Klebsiella pneumoniae (12.5 mu M), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that Ga-67-D2 is taken up more efficiently than (67)-Ga-citrate. In naive mice, Ga-67-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.

  DOI：

  10.1021/acs.jmedchem.9b01388
• 作为产物：
  描述：

  环丙沙星 在 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 48.17h， 生成 desferrioxamine
  参考文献：
  名称：

  Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency

  摘要：

  Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using small-molecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 mu M in Escherichia con, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 mu M), Staphylococcus aureus (0.94 mu M), and Klebsiella pneumoniae (12.5 mu M), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that Ga-67-D2 is taken up more efficiently than (67)-Ga-citrate. In naive mice, Ga-67-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.

  DOI：

  10.1021/acs.jmedchem.9b01388

文献信息

• Chemical syntheses and in vitro antibacterial activity of two desferrioxamine B-ciprofloxacin conjugates with potential esterase and phosphatase triggered drug release linkers
  作者：Cheng Ji、Marvin J. Miller

  DOI：10.1016/j.bmc.2012.04.034

  日期：2012.6

  Two desferrioxamine B-ciprofloxacin conjugates with 'trimethyl-lock' based linkers that are designed to release the antibiotic after esterase or phosphatase-mediated hydrolysis were synthesized. The potential esterase-sensitive conjugate 13 displayed moderate to good antibacterial activities against selected ferrioxamine-utilizing bacteria, although the activities were lower than the parent drug ciprofloxacin. However, the potential phophatase-sensitive conjugate 23 was inactive against the same panel of organisms tested. These properties appeared to be related to the activating efficiency of the linker by the enzyme and to the outer membrane protein recognition of the chemically modified siderophore used in the conjugate. (C) 2012 Elsevier Ltd. All rights reserved.
• Theranostic Gallium Siderophore Ciprofloxacin Conjugate with Broad Spectrum Antibiotic Potency
  作者：Apurva Pandey、Chloé Savino、Shin Hye Ahn、Zhaoyong Yang、Steven G. Van Lanen、Eszter Boros

  DOI：10.1021/acs.jmedchem.9b01388

  日期：2019.11.14

  Pathogenic bacteria scavenge ferric iron from the host for survival and proliferation using small-molecular chelators, siderophores. Here, we introduce and assess the gallium(III) complex of ciprofloxacin-functionalized desferrichrome (D2) as a potential therapeutic for bacterial infection using an in vitro assay and radiochemical, tracer-based approach. Ga-D2 exhibits a minimum inhibitory concentration of 0.23 mu M in Escherichia con, in line with the parent fluoroquinolone antibiotic. Competitive and mutant strain assays show that Ga-D2 relies on FhuA-mediated transport for internalization. Ga-D2 is potent against Pseudomonas aeruginosa (3.8 mu M), Staphylococcus aureus (0.94 mu M), and Klebsiella pneumoniae (12.5 mu M), while Fe-D2 is inactive in these strains. Radiochemical experiments with E. coli reveal that Ga-67-D2 is taken up more efficiently than (67)-Ga-citrate. In naive mice, Ga-67-D2 clears renally and is excreted 13% intact in the urine. These pharmacokinetic and bacterial growth inhibitory properties qualify Ga-D2 for future investigations as a diagnosis and treatment tool for infection.