Design, synthesis and evaluation of triazole functionalized ring-fused 2-pyridones as antibacterial agents
Design, synthesis and evaluation of triazole functionalized ring-fused 2-pyridones as antibacterial agents
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DOI：
10.1016/j.ejmech.2012.06.018
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发表时间：
2012-08-01
影响因子：
6.7
通讯作者：
Almqvist, Fredrik
中科院分区：
文献类型：
--
作者：
Bengtsson, Christoffer;Lindgren, Anders E. G.;Almqvist, Fredrik
抗菌素耐药性是当今一个世界性的问题，对具有新作用模式的新型抗菌剂的需求是巨大的。在努力寻找新的抗菌剂来抑制菌毛组装(一种重要的毒力因子)的过程中，已经开发了在环稠合的双环2-吡啶酮的8和2位引入三氮唑的路线。这是通过Sonogashira偶联，然后是惠斯根1，3-偶极环加成得到的。该方法的发展使引入一系列不同的取代三氮唑成为可能，并在全细胞菌毛依赖生物膜试验中测试了它们的抗菌性能。在测试的24个候选化合物中，大多数显示出低活性或没有活性，但有趣的是，三个化合物，一个8-取代和两个2-取代，显示出良好的活性，EC50‘S在9到50亩之间。(C)2012爱思唯尔·马森SAS。版权所有。
Antibacterial resistance is today a worldwide problem and the demand for new classes of antibacterial agents with new mode of action is enormous. In the strive for new antibacterial agents that inhibit pilus assembly, an important virulence factor, routes to introduce triazoles in position 8 and 2 of ring-fused bicyclic 2-pyridones have been developed. This was made via Sonogashira couplings followed by Huisgen 1,3-dipolar cycloadditions. The method development made it possible to introduce a diverse series of substituted triazoles and their antibacterial properties were tested in a whole cell pili-dependent biofilm assay. Most of the twenty four candidates tested showed low to no activity but interestingly three compounds, one 8-substituted and two 2-substituted, showed promising activities with EC50's between 9 and 50 mu M. (C) 2012 Elsevier Masson SAS. All rights reserved.