1-Cyclopropyl-6-fluoro-7-[4-[4-[hydroxy-[5-[[4-[hydroxy-[5-[[4-[hydroxy(5-hydroxypentyl)amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid | 1422350-15-9

• 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: 1-Cyclopropyl-6-fluoro-7-[4-[4-[hydroxy-[5-[[4-[hydroxy-[5-[[4-[hydroxy(5-hydroxypentyl)amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid
• 英文别名: 1-cyclopropyl-6-fluoro-7-[4-[4-[hydroxy-[5-[[4-[hydroxy-[5-[[4-[hydroxy(5-hydroxypentyl)amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid
• CAS: 1422350-15-9
• 化学式: C₄₄H₆₅FN₈O₁₃
• 分子量: 933.044
• InChiKey: KSBYHOAXOJFYMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  66
• 可旋转键数：
  29
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  281
• 氢给体数：
  7
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-(4-(8,19,30-tris(benzyloxy)-9,12,20,23,31-pentaoxo-1-phenyl-2-oxa-8,13,19,24,30-pentaazatetratriacontan-34-oyl)piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以97%的产率得到1-Cyclopropyl-6-fluoro-7-[4-[4-[hydroxy-[5-[[4-[hydroxy-[5-[[4-[hydroxy(5-hydroxypentyl)amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]amino]pentyl]amino]-4-oxobutanoyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  Trihydroxamate Siderophore–Fluoroquinolone Conjugates Are Selective Sideromycin Antibiotics that Target Staphylococcus aureus

  摘要：

  Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a "Trojan horse" fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a beta-lactam carbacepholosporin, Lorabid, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic toward Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 mu M for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents.

  DOI：

  10.1021/bc300610f

文献信息

• Trihydroxamate Siderophore–Fluoroquinolone Conjugates Are Selective Sideromycin Antibiotics that Target Staphylococcus aureus
  作者：Timothy A. Wencewicz、Timothy E. Long、Ute Möllmann、Marvin J. Miller

  DOI：10.1021/bc300610f

  日期：2013.3.20

  Siderophores are multidentate iron(III) chelators used by bacteria for iron assimilation. Sideromycins, also called siderophore-antibiotic conjugates, are a unique subset of siderophores that enter bacterial cells via siderophore uptake pathways and deliver the toxic antibiotic in a "Trojan horse" fashion. Sideromycins represent a novel antibiotic delivery technology with untapped potential for developing sophisticated microbe-selective antibacterial agents that limit the emergence of bacterial resistance. The chemical synthesis of a series of mono-, bis-, and trihydroxamate sideromycins are described here along with their biological evaluation in antibacterial susceptibility assays. The linear hydroxamate siderophores used for the sideromycins in this study were derived from the ferrioxamine family and inspired by the naturally occurring salmycin sideromycins. The antibacterial agents used were a beta-lactam carbacepholosporin, Lorabid, and a fluoroquinolone, ciprofloxacin, chosen for the different locations of their biological targets, the periplasm (extracellular) and the cytoplasm (intracellular). The linear hydroxamate-based sideromycins were selectively toxic toward Gram-positive bacteria, especially Staphylococcus aureus SG511 (MIC = 1.0 mu M for the trihydroxamate-fluoroquinolone sideromycin). Siderophore-sideromycin competition assays demonstrated that only the fluoroquinolone sideromycins required membrane transport to reach their cytoplasmic biological target and that a trihydroxamate siderophore backbone was required for protein-mediated active transport of the sideromycins into S. aureus cells via siderophore uptake pathways. This work represents a comprehensive study of linear hydroxamate sideromycins and teaches how to build effective hydroxamate-based sideromycins as Gram-positive selective antibiotic agents.