Revisiting AI-2 quorum sensing inhibitors: direct comparison of alkyl-DPD analogues and a natural product fimbrolide.
Revisiting AI-2 quorum sensing inhibitors: direct comparison of alkyl-DPD analogues and a natural product fimbrolide.
复制标题
DOI：
10.1021/ja9066783
复制
发表时间：
2009-11-04
影响因子：
15
通讯作者：
Janda, Kim D.
中科院分区：
文献类型：
--
作者：
Lowery, Colin A.;Abe, Takumi;Park, Junguk;Eubanks, Lisa M.;Sawada, Daisuke;Kaufmann, Gunnar F.;Janda, Kim D.
群体感应（QS）系统已被提出在各种各样的细菌。基于AI-2的QS系统代表了这些提出的种间系统中研究最多的，并且已被证明可以调节多种功能，例如生物发光、毒力因子的表达和生物膜形成。因此，激动剂和拮抗剂的调节化合物的开发对于未知的基于AI-2的QS系统的研究和细菌感染的潜在治疗具有极大的意义。fimbrolide类天然产物对基于AI-2的QS表现出优异的抑制活性，因此可以被认为是AI-2抑制剂的“金标准”。因此，我们试图包括芬布罗利特作为我们最近开发的AI-2调节剂的烷基-DPD组的对照化合物。在此，我们提出了一个修订的合成一个共同研究的fimbrolide，以及fimbrolide和烷基-DPD类似物之间的直接比较。我们证明，我们的烷基-DPD类似物是更有效的抑制剂的QS在哈氏弧菌和鼠伤寒沙门氏菌，两种生物体与定义的AI-2系统，并在这样做，提出了问题的广泛接受的使用fimbrolide衍生的化合物作为AI-2抑制的“金标准”。
Quorum sensing (QS) systems have been proposed in a wide variety of bacteria. The AI-2-based QS system represents the most studied of these proposed interspecies systems, and has been shown to regulate diverse functions such as bioluminescence, expression of virulence factors, and biofilm formation. As such, the development of modulatory compounds, both agonists and antagonists, is of great interest for the study of unknown AI-2 based QS systems and the potential treatment of bacterial infections. The fimbrolide class of natural products has exhibited excellent inhibitory activity against AI-2-based QS, and as such may be considered the “gold-standard” of AI-2 inhibitors. Thus, we sought to include a fimbrolide as a control compound for our recently developed alkyl-DPD panel of AI-2 modulators. Herein, we present a revised synthesis of a commonly studied fimbrolide, as well as a direct comparison between the fimbrolide and alkyl-DPD analogs. We demonstrate that our alkyl-DPD analogs are more potent inhibitors of QS in both Vibrio harveyi and Salmonella typhimurium, the two organisms with defined AI-2 systems, and in doing so, call into question the widely accepted use of fimbrolide-derived compounds as the “gold standard” of AI-2 inhibition.
登录
查看更多内容
影响因子：
4.9
作者：
Kuehl, Richard;Al-Bataineh, Sameer;Landmann, Regine
通讯作者：
Landmann, Regine
影响因子：
5.1
作者：
Defoirdt, Tom;Miyamoto, Carol M.;Bossier, Peter
通讯作者：
Bossier, Peter
影响因子：
2.1
作者：
Manny, AJ;Kjelleberg, S;Steinberg, P
通讯作者：
Steinberg, P
影响因子：
5
作者：
Ren, DC;Zuo, RJ;Wood, TK
通讯作者：
Wood, TK
影响因子：
2.7
作者：
Ganin, Hadas;Tang, Xu;Meijler, Michael M.
通讯作者：
Meijler, Michael M.