School of Chemistry, Faculty of Science, The University of New South Wales, Sydney, NSW 2052, Australia.
Singapore Centre for Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore.
Molecules. 2020 Jul 7;25(13):3103. doi: 10.3390/molecules25133103.
The quinolone system (PQS) is one of the three major interconnected quorum sensing signaling systems in . The virulence factors PQS and HHQ activate the transcription regulator PqsR (MvfR), which controls several activities in bacteria, including biofilm formation and upregulation of PQS biosynthesis. The enzyme anthraniloyl-CoA synthetase (PqsA) catalyzes the first and critical step in the biosynthesis of quinolones; therefore, it is an attractive target for the development of anti-virulence therapeutics against resistance. Herein, we report the design and synthesis of novel triazole nucleoside-based anthraniloyl- adenosine monophosphate (AMP) mimics. These analogues had a major impact on the morphology of bacterial biofilms and caused significant reduction in bacterial aggregation and population density. However, the compounds showed only limited inhibition of PQS and did not exhibit any effect on pyocyanin production.
群体感应系统（PQS）是 中三大相互关联的群体感应信号系统之一。毒力因子 PQS 和 HHQ 激活转录调节因子 PqsR（MvfR），该因子控制细菌中的几种活性，包括生物膜形成和 PQS 生物合成的上调。酶邻氨甲酰辅酶 A 合酶（PqsA）催化喹诺酮生物合成的第一步和关键步骤；因此，它是开发针对 耐药性的抗毒力治疗药物的有吸引力的靶标。本文报道了新型三唑核苷基邻氨甲酰腺苷一磷酸（AMP）类似物的设计和合成。这些类似物对细菌生物膜的形态有重大影响，并导致细菌聚集和种群密度显著降低。然而，这些化合物对 PQS 的抑制作用有限，对绿脓菌素的产生没有任何影响。
