Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance

The Pseudomonas quinolone system (PQS) is one of the three major interconnected quorum sensing signaling systems in Pseudomonas aeruginosa. The virulence factors PQS and HHQ activate the transcription regulator PqsR (MvfR), which controls several activities in bacteria, including biofilm formation a...

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Bibliographic Details
Main Authors: Sabir, Shekh, Subramoni, Sujatha, Das, Theerthankar, Black, David StC, Rice, Scott A., Kumar, Naresh
Other Authors: Singapore Centre for Environmental Life Sciences and Engineering
Format: Article
Language:English
Published: 2021
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Online Access:https://hdl.handle.net/10356/146344
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Institution: Nanyang Technological University
Language: English
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Summary:The Pseudomonas quinolone system (PQS) is one of the three major interconnected quorum sensing signaling systems in Pseudomonas aeruginosa. 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 Pseudomonas 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.