Substituted lactam and cyclic azahemiacetals modulate Pseudomonas aeruginosa quorum sensing.
Substituted lactam and cyclic azahemiacetals modulate Pseudomonas aeruginosa quorum sensing.
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DOI：
10.1016/j.bmc.2011.07.044
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发表时间：
2011-09-15
影响因子：
3.5
通讯作者：
Wnuk, Stanislaw F.
中科院分区：
文献类型：
--
作者：
Malladi, Venkata L. A.;Sobczak, Adam J.;Maricic, Natalie;Murugapiran, Senthil Kumar;Schneper, Lisa;Makemson, John;Mathee, Kalai;Wnuk, Stanislaw F.
群体感应（QS）是细菌用来控制多个过程的群体依赖性信号传导过程，包括对建立感染至关重要的毒力。革兰氏阴性菌使用的最常见的QS信号分子是酰基高丝氨酸内酯。非天然酰基高丝氨酸内酯（AHL）配体的发展已成为一个有前途的新策略，以抑制QS在革兰氏阴性菌。在这项工作中，我们合成了一组光学纯的γ-内酰胺及其还原的环状氮杂半缩醛类似物，带有额外的烷基硫甲基取代基，并评估了它们对AHL依赖的铜绿假单胞菌las和rhl QS途径的影响。这些配体的浓度和简单的结构修饰如烷硫基取代基的长度对活性有显著影响。具有壬基硫基或十二烷基硫基链的γ-内酰胺衍生物作为具有中等效力的las信号传导抑制剂。发现具有较短丙硫基或己硫基取代基的环状氮杂半缩醛在较高浓度下强烈抑制las和rhl信号传导，而丙硫基类似物在较低浓度下强烈刺激las QS系统。
Quorum sensing (QS) is a population-dependent signaling process bacteria use to control multiple processes including virulence that is critical for establishing infection. The most common QS signaling molecule used by Gram-negative bacteria are acylhomoserine lactones. The development of non-native acylhomoserine lactone (AHL) ligands has emerged as a promising new strategy to inhibit QS in Gram-negative bacteria. In this work, we have synthesized a set of optically pure γ-lactams and their reduced cyclic azahemiacetal analogues, bearing the additional alkylthiomethyl substituent, and evaluated their effect on the AHL-dependent Pseudomonas aeruginosa las and rhl QS pathways. The concentration of these ligands and the simple structural modification such as the length of the alkylthio substituent has notable effect on activity. The γ-lactam derivatives with nonylthio or dodecylthio chains acted as inhibitors of las signaling with moderate potency. The cyclic azahemiacetal with shorter propylthio or hexylthio substituent was found to strongly inhibit both las and rhl signaling at higher concentrations while the propylthio analogue strongly stimulated the las QS system at lower concentrations.
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影响因子：
15
作者：
Amara, Neri;Mashiach, Roi;Meijler, Michael M.
通讯作者：
Meijler, Michael M.
影响因子：
4.4
作者：
Ishida, Takenori;Ikeda, Tsukasa;Kato, Junichi
通讯作者：
Kato, Junichi
影响因子：
3.2
作者：
Pearson, JP;Pesci, EC;Iglewski, BH
通讯作者：
Iglewski, BH
影响因子：
4.4
作者：
Morohoshi, Tornohiro;Shiono, Toshitaka;Ikeda, Tsukasa
通讯作者：
Ikeda, Tsukasa
DOI：
10.1124/jpet.104.075150
发表时间：
2005-02-01
影响因子：
3.5
作者：
Raffa, RB;Iannuzzo, JR;Young, JM
通讯作者：
Young, JM