Design, Synthesis and Biological Evaluation of Novel Anthraniloyl-AMP Mimics as PQS Biosynthesis Inhibitors Against Pseudomonas aeruginosa Resistance.

Sabir, S; Subramoni, S; Das, T; Black, DS; Rice, SA; Kumar, N

Design, Synthesis and Biological Evaluation of Novel Anthraniloyl-AMP Mimics as PQS Biosynthesis Inhibitors Against Pseudomonas aeruginosa Resistance.

Sabir, S Subramoni, S Das, T Black, DS Rice, SA Kumar, N

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Publisher:: MDPI AG
Publication Type:: Journal Article
Citation:: Molecules (Basel, Switzerland), 2020, 25, (13), pp. 3103-3103
Issue Date:: 2020-07-07

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Field	Value	Language
dc.contributor.author	Sabir, S
dc.contributor.author	Subramoni, S
dc.contributor.author	Das, T
dc.contributor.author	Black, DS
dc.contributor.author	Rice, SA
dc.contributor.author	Kumar, N
dc.date.accessioned	2020-08-18T06:48:22Z
dc.date.available	2020-07-02
dc.date.available	2020-08-18T06:48:22Z
dc.date.issued	2020-07-07
dc.identifier.citation	Molecules (Basel, Switzerland), 2020, 25, (13), pp. 3103-3103
dc.identifier.issn	1420-3049
dc.identifier.issn	1420-3049
dc.identifier.uri	http://hdl.handle.net/10453/142201
dc.description.abstract	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.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI AG
dc.relation.ispartof	Molecules (Basel, Switzerland)
dc.relation.isbasedon	10.3390/molecules25133103
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 0307 Theoretical and Computational Chemistry
dc.subject.classification	Organic Chemistry
dc.title	Design, Synthesis and Biological Evaluation of Novel Anthraniloyl-AMP Mimics as PQS Biosynthesis Inhibitors Against Pseudomonas aeruginosa Resistance.
dc.type	Journal Article
utslib.citation.volume	25
utslib.location.activity	Switzerland
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0305 Organic Chemistry
utslib.for	0307 Theoretical and Computational Chemistry
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	open_access	*
dc.date.updated	2020-08-18T06:47:57Z
pubs.issue	13
pubs.publication-status	Published
pubs.volume	25
utslib.citation.issue	13

Abstract:

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.

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http://hdl.handle.net/10453/142201