(Z)-4-bromo-5-(bromomethylene)-1-dodecyl-1H-pyrrol-2-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: (Z)-4-bromo-5-(bromomethylene)-1-dodecyl-1H-pyrrol-2-one
• 英文别名: (5Z)-4-bromo-5-(bromomethylidene)-1-dodecylpyrrol-2-one
• 化学式: C₁₇H₂₇Br₂NO
• 分子量: 421.215
• InChiKey: AQSDKVBESWJLIN-PEZBUJJGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  21
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  1-氨基癸烷 在 对甲苯磺酸 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 3.0h， 生成 (Z)-4-bromo-5-(bromomethylene)-1-dodecyl-1H-pyrrol-2-one
  参考文献：
  名称：

  Synthesis, quorum sensing inhibition and docking studies of 1,5-dihydropyrrol-2-ones

  摘要：

  Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli use N-acylated L-homoserine lactones (AHLs) as autoinducers (AIs) for quorum sensing (QS), a chief regulatory and cell-to-cell communication system. QS is responsible for social adaptation, virulence factor production, biofilm production and antibiotic resistance in bacteria. Fimbrolides, a class of halogenated furanones isolated from the red marine alga Delisea pulchra, have been shown to exhibit promising QS inhibitory activity against various Gram-negative and Gram-positive bacterial strains. In this work, various lactam analogues of fimbrolides viz., 1,5-dihydropyrrol-2-ones, were designed and synthesized via an efficient lactamization protocol. All the synthesized analogues were tested for QS inhibition against the E. coli AHL-monitor strain JB357 gfp (ASV). Compound 17a emerged as the most potent compound, followed by 9c, with AIC(40) values (the ratio of synthetic inhibitor to natural AHL signaling molecule that is required to lower GFP expression to 40%) of 1.95 and 19.00, respectively. Finally, the potential binding interactions between the synthesized molecules and the LasR QS receptor were studied by molecular docking. Our results indicate that 1,5-dihydropyrrol-2-ones have the ability to serve as potential leads for the further development of novel QS inhibitors as antimicrobial therapeutics. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.10.025

文献信息

• Synthesis, quorum sensing inhibition and docking studies of 1,5-dihydropyrrol-2-ones
  作者：Wai-Kean Goh、Christopher R. Gardner、Kondapalli V.G. Chandra Sekhar、Nripendra N. Biswas、Shashidhar Nizalapur、Scott A. Rice、Mark Willcox、David StC. Black、Naresh Kumar

  DOI：10.1016/j.bmc.2015.10.025

  日期：2015.12

  Gram-negative bacteria such as Pseudomonas aeruginosa and Escherichia coli use N-acylated L-homoserine lactones (AHLs) as autoinducers (AIs) for quorum sensing (QS), a chief regulatory and cell-to-cell communication system. QS is responsible for social adaptation, virulence factor production, biofilm production and antibiotic resistance in bacteria. Fimbrolides, a class of halogenated furanones isolated from the red marine alga Delisea pulchra, have been shown to exhibit promising QS inhibitory activity against various Gram-negative and Gram-positive bacterial strains. In this work, various lactam analogues of fimbrolides viz., 1,5-dihydropyrrol-2-ones, were designed and synthesized via an efficient lactamization protocol. All the synthesized analogues were tested for QS inhibition against the E. coli AHL-monitor strain JB357 gfp (ASV). Compound 17a emerged as the most potent compound, followed by 9c, with AIC(40) values (the ratio of synthetic inhibitor to natural AHL signaling molecule that is required to lower GFP expression to 40%) of 1.95 and 19.00, respectively. Finally, the potential binding interactions between the synthesized molecules and the LasR QS receptor were studied by molecular docking. Our results indicate that 1,5-dihydropyrrol-2-ones have the ability to serve as potential leads for the further development of novel QS inhibitors as antimicrobial therapeutics. (C) 2015 Elsevier Ltd. All rights reserved.