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Design, Synthesis and Biological Evaluation of Novel Anthraniloyl-AMP Mimics as PQS Biosynthesis Inhibitors Against <i>Pseudomonas aeruginosa</i> Resistance
oleh: Shekh Sabir, Sujatha Subramoni, Theerthankar Das, David StC. Black, Scott A. Rice, Naresh Kumar
| Format: | Article |
|---|---|
| Diterbitkan: | MDPI AG 2020-07-01 |
Deskripsi
The <i>Pseudomonas</i> quinolone system (PQS) is one of the three major interconnected quorum sensing signaling systems in <i>Pseudomonas aeruginosa</i>. 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 <i>Pseudomonas</i> 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.