O-benzyl-ciprofloxacin hydrochloride | 1422350-03-5

• 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: O-benzyl-ciprofloxacin hydrochloride
• CAS: 1422350-03-5
• 化学式: C₂₄H₂₄FN₃O₃*ClH
• 分子量: 457.932
• InChiKey: GKYOMXLHQPAFSX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.66
• 重原子数：
  32.0
• 可旋转键数：
  5.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  63.57
• 氢给体数：
  1.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  O-benzyl-ciprofloxacin hydrochloride 、 C₂₈H₄₃N₅O₁₂S 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以84 %的产率得到C₅₂H₆₅FN₈O₁₄S
  参考文献：
  名称：

  铜绿假单胞菌激活的凝集素靶向前药用于自毁性抗生素释放

  摘要：

  慢性铜绿假单胞菌感染的特征是生物膜形成，这是铜绿假单胞菌的主要毒力因子和广泛耐药性的原因。氟喹诺酮类药物是有效的抗生素，但与严重的副作用有关。两个细胞外铜绿假单胞菌特异性凝集素 LecA 和 LecB 是生物膜的关键结构成分，可用于靶向药物递送。在这项工作中，几种氟喹诺酮类药物通过可裂解的肽接头与凝集素探针结合，产生凝集素靶向前药。因此，从机制上讲，这些缀合物在全身分布中保持无毒，并且只有在它们在感染部位积聚后才会被激活以杀死。合成的前药在宿主血浆和肝脏代谢存在的情况下被证明是稳定的，但在铜绿假单胞菌存在的情况下迅速释放抗生素货物在体外以自我毁灭的方式。此外，前药在体外显示出良好的吸收、分布、代谢和消除 (ADME) 特性并降低了毒性，从而建立了第一个针对铜绿假单胞菌的凝集素靶向抗生素前药。

  DOI：

  10.1021/acs.jmedchem.2c01214
• 作为产物：
  描述：

  溴甲苯 在 盐酸 、 potassium hydrogencarbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.5h， 生成 O-benzyl-ciprofloxacin hydrochloride
  参考文献：
  名称：

  铜绿假单胞菌激活的凝集素靶向前药用于自毁性抗生素释放

  摘要：

  慢性铜绿假单胞菌感染的特征是生物膜形成，这是铜绿假单胞菌的主要毒力因子和广泛耐药性的原因。氟喹诺酮类药物是有效的抗生素，但与严重的副作用有关。两个细胞外铜绿假单胞菌特异性凝集素 LecA 和 LecB 是生物膜的关键结构成分，可用于靶向药物递送。在这项工作中，几种氟喹诺酮类药物通过可裂解的肽接头与凝集素探针结合，产生凝集素靶向前药。因此，从机制上讲，这些缀合物在全身分布中保持无毒，并且只有在它们在感染部位积聚后才会被激活以杀死。合成的前药在宿主血浆和肝脏代谢存在的情况下被证明是稳定的，但在铜绿假单胞菌存在的情况下迅速释放抗生素货物在体外以自我毁灭的方式。此外，前药在体外显示出良好的吸收、分布、代谢和消除 (ADME) 特性并降低了毒性，从而建立了第一个针对铜绿假单胞菌的凝集素靶向抗生素前药。

  DOI：

  10.1021/acs.jmedchem.2c01214

文献信息

• Conjugates of Iron-Transporting N-Hydroxylactams with Ciprofloxacin
  作者：Olga Bakulina、Anton Bannykh、Ekaterina Levashova、Mikhail Krasavin

  DOI：10.3390/molecules27123910

  日期：——

  Screening of a library of novel N-hydroxylactams amenable by the Castagnoli-Cushman reaction identified four lead compounds that facilitated 55Fe transport into P. aeruginosa cells (one of these synthetic siderophores was found to be as efficient at promoting iron uptake as the natural siderophores pyoverdine, pyochelin or enterobactin). Conjugates of the four lead siderophores with ciprofloxacin were tested for antibacterial activity against P. aeruginosa POA1 (wild type) and the ∆pvdF∆pchA mutant strain. The antibacterial activity was found to be pronounced against the ∆pvdF∆pchA mutant strain grown in CAA medium but not for the POA1 strain. This may be indicative of these compounds being ‘Trojan horse’ antibiotics. Further scrutiny of the mechanism of the antibacterial action of the newly developed conjugates is warranted.

  筛选一批新型N-羟基内酰胺库，通过Castagnoli-Cushman反应鉴定出四种引导化合物，可以促进55Fe进入P. aeruginosa细胞（其中一种合成铁载体与天然铁载体pyoverdine、pyochelin或enterobactin一样有效）。将这四种铁载体与环丙沙星结合，对P. aeruginosa POA1（野生型）和∆pvdF∆pchA突变株进行抗菌活性测试。发现抗菌活性对在CAA培养基中生长的∆pvdF∆pchA突变株非常显著，但对POA1株没有。这可能表明这些化合物是“特洛伊木马”抗生素。有必要进一步研究新开发的铁载体与抗生素结合物的抗菌作用机制。
• 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.
• Biscatecholate–Monohydroxamate Mixed Ligand Siderophore–Carbacephalosporin Conjugates are Selective Sideromycin Antibiotics that Target Acinetobacter baumannii
  作者：Timothy A. Wencewicz、Marvin J. Miller

  DOI：10.1021/jm400265k

  日期：2013.5.23

  Chemical syntheses and biological evaluation of biscatecholate-monohydroxamate mixed ligand sideromycins utilizing the carbacephalosporin beta-lactam antibiotic loracarbef and the fluoroquinolone antibiotic ciprofloxacin are described. The mixed ligand beta-lactam sideromycin (1b) had remarkably selective and extremely potent antibacterial activity against the Gram-negative pathogen Acinetobacter baumannii ATCC 17961 (MIC = 0.0078 mu M). The antibacterial activity of the beta-lactam sideromycin was inversely related to the iron(III) concentration in the testing media and was antagonized by the presence of the competing parent siderophore. These data suggested that active transport of the mixed ligand beta-lactam sideromycin across the outer cell membrane of A. baumannii via siderophore-uptake pathways was responsible for the selective and potent antibacterial activity.