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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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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spelling sg-ntu-dr.10356-1463442021-02-13T20:15:52Z Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance Sabir, Shekh Subramoni, Sujatha Das, Theerthankar Black, David StC Rice, Scott A. Kumar, Naresh Singapore Centre for Environmental Life Sciences and Engineering Science::Chemistry Pseudomonas Quinolone System Quorum Sensing 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. Published version 2021-02-10T04:45:18Z 2021-02-10T04:45:18Z 2020 Journal Article Sabir, S., Subramoni, S., Das, T., Black, D. S., Rice, S. A., & Kumar, N. (2020). Design, Synthesis and Biological Evaluation of Novel Anthraniloyl-AMP Mimics as PQS Biosynthesis Inhibitors Against Pseudomonas aeruginosa Resistance. Molecules, 25(13), 3103-. doi:10.3390/molecules25133103 1420-3049 https://hdl.handle.net/10356/146344 10.3390/molecules25133103 32646050 2-s2.0-85087841987 13 25 en Molecules © 2020 The Authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Chemistry
Pseudomonas Quinolone System
Quorum Sensing
spellingShingle Science::Chemistry
Pseudomonas Quinolone System
Quorum Sensing
Sabir, Shekh
Subramoni, Sujatha
Das, Theerthankar
Black, David StC
Rice, Scott A.
Kumar, Naresh
Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance
description 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.
author2 Singapore Centre for Environmental Life Sciences and Engineering
author_facet Singapore Centre for Environmental Life Sciences and Engineering
Sabir, Shekh
Subramoni, Sujatha
Das, Theerthankar
Black, David StC
Rice, Scott A.
Kumar, Naresh
format Article
author Sabir, Shekh
Subramoni, Sujatha
Das, Theerthankar
Black, David StC
Rice, Scott A.
Kumar, Naresh
author_sort Sabir, Shekh
title Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance
title_short Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance
title_full Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance
title_fullStr Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance
title_full_unstemmed Design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as PQS biosynthesis inhibitors against pseudomonas aeruginosa resistance
title_sort design, synthesis and biological evaluation of novel anthraniloyl-amp mimics as pqs biosynthesis inhibitors against pseudomonas aeruginosa resistance
publishDate 2021
url https://hdl.handle.net/10356/146344
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