(S)-3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione | 1370024-33-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: (S)-3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione
• 英文别名: (S)-3-decanoyl-5-(2-hydroxyethyl)tetramic acid；tetramic acid
• CAS: 1370024-33-1
• 化学式: C₁₆H₂₇NO₄
• 分子量: 297.395
• InChiKey: OSWGMRUTKTWVOY-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.39
• 重原子数：
  21.0
• 可旋转键数：
  10.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  86.63
• 氢给体数：
  3.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  3-氧代-N-[(3S)-四氢-2-氧代-3-呋喃基]十二酰胺 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以68%的产率得到(S)-3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione
  参考文献：
  名称：

  Targeting Staphylococcus aureus Quorum Sensing with Nonpeptidic Small Molecule Inhibitors

  摘要：

  A series of 3-oxo-C12-HSL, tetramic acid, and tetronic acid analogues were synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were noncompetitive inhibitors of the autoinducing peptide (AIP) activated AgrC receptor, by altering the activation efficacy of the cognate AIP-1. They appeared to act as negative allosteric modulators and are exemplified by 3-tetradecanoyltetronic acid 17, which reduced nasal cell colonization and arthritis in a murine infection model.

  DOI：

  10.1021/jm500215s

文献信息

• Defining the Mode of Action of Tetramic Acid Antibacterials Derived from Pseudomonas aeruginosa Quorum Sensing Signals
  作者：Colin A. Lowery、Junguk Park、Christian Gloeckner、Michael M. Meijler、Ryan S. Mueller、Helena I. Boshoff、Ricky L. Ulrich、Clifton E. Barry,、Douglas H. Bartlett、Vladimir V. Kravchenko、Gunnar F. Kaufmann、Kim D. Janda

  DOI：10.1021/ja9056079

  日期：2009.10.14

  In nature, bacteria rarely exist as single, isolated entities, but rather as communities comprised of many other species including higher host organisms. To survive in these competitive environments, microorganisms have developed elaborate tactics such as the formation of biofilms and the production of antimicrobial toxins. Recently, it was discovered that the Gram-negative bacterium Pseudomonas aeruginosa, an opportunistic human pathogen, produces an antibiotic, 3-(1-hydroxydecylidene)-5-(2-hydroxyethyl)pyrrolidine-2,4-dione (C-12-TA), derived from one of its quorum sensing molecules. Here, we present a comprehensive study of the expanded spectrum Of C-12-TA antibacterial activity against microbial competitors encountered by P. aeruginosa in nature as well as significant human pathogens. The mechanism of action Of C-12-TA was also elucidated, and C-12-TA was found to dissipate both the membrane potential and the pH gradient of Gram-positive bacteria, correlating well with cell death. Notably, in stark contrast to its parent molecule 3-oxo-dodecanoyl homoserine lactone (3-oxo-C-12-HSL), neither activation of cellular stress pathways nor cytotoxicity was observed in human cells treated with C-12-TA. Our results suggest that the QS machinery of P. aeruginosa has evolved for a dual-function, both to signal others of the same species and also to defend against host immunity and competing bacteria. Because of the broad-spectrum antibacterial activity, established mode of action, lack of rapid resistance development, and tolerance by human cells, the C-12-TA scaffold may also serve as a new lead compound for the development of antimicrobial therapeutics.