Thioether-linked dihydropyrrol-2-one analogues as PqsR antagonists against antibiotic resistant Pseudomonas aeruginosa.

Sabir, S; Suresh, D; Subramoni, S; Das, T; Bhadbhade, M; Black, DS; Rice, SA; Kumar, N

Thioether-linked dihydropyrrol-2-one analogues as PqsR antagonists against antibiotic resistant Pseudomonas aeruginosa.

Sabir, S Suresh, D Subramoni, S Das, T Bhadbhade, M Black, DS Rice, SA Kumar, N

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Publisher:: PERGAMON-ELSEVIER SCIENCE LTD
Publication Type:: Journal Article
Citation:: Bioorganic & medicinal chemistry, 2021, 31, pp. 115967
Issue Date:: 2021-02

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Field	Value	Language
dc.contributor.author	Sabir, S
dc.contributor.author	Suresh, D
dc.contributor.author	Subramoni, S
dc.contributor.author	Das, T
dc.contributor.author	Bhadbhade, M
dc.contributor.author	Black, DS
dc.contributor.author	Rice, SA
dc.contributor.author	Kumar, N
dc.date.accessioned	2021-04-14T05:54:05Z
dc.date.available	2020-12-18
dc.date.available	2021-04-14T05:54:05Z
dc.date.issued	2021-02
dc.identifier.citation	Bioorganic & medicinal chemistry, 2021, 31, pp. 115967
dc.identifier.issn	0968-0896
dc.identifier.issn	1464-3391
dc.identifier.uri	http://hdl.handle.net/10453/148095
dc.description.abstract	The Pseudomonas quinolone system (pqs) is one of the key quorum sensing systems in antibiotic-resistant P. aeruginosa and is responsible for the production of virulence factors and biofilm formation. Thus, synthetic small molecules that can target the PqsR (MvfR) receptor can be utilized as quorum sensing inhibitors to treat P. aeruginosa infections. In this study, we report the synthesis of novel thioether-linked dihydropyrrol-2-one (DHP) analogues as PqsR antagonists. Compound 7g containing a 2-mercaptopyridyl linkage effectively inhibited the pqs system with an IC<sub>50</sub> of 32 µM in P. aeruginosa PAO1. Additionally, these inhibitors significantly reduced bacterial aggregation and biofilm formation without affecting planktonic growth. The molecular docking study suggest that these inhibitors bind with the ligand binding domain of the MvfR as a competitive antagonist.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	PERGAMON-ELSEVIER SCIENCE LTD
dc.relation.ispartof	Bioorganic & medicinal chemistry
dc.relation.isbasedon	10.1016/j.bmc.2020.115967
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences
dc.subject.classification	Medicinal & Biomolecular Chemistry
dc.title	Thioether-linked dihydropyrrol-2-one analogues as PqsR antagonists against antibiotic resistant Pseudomonas aeruginosa.
dc.type	Journal Article
utslib.citation.volume	31
utslib.location.activity	England
utslib.for	0304 Medicinal and Biomolecular Chemistry
utslib.for	0305 Organic Chemistry
utslib.for	1115 Pharmacology and Pharmaceutical Sciences
pubs.organisational-group	/University of Technology Sydney
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
utslib.copyright.status	closed_access	*
dc.date.updated	2021-04-14T05:54:04Z
pubs.publication-status	Published
pubs.volume	31

Abstract:

The Pseudomonas quinolone system (pqs) is one of the key quorum sensing systems in antibiotic-resistant P. aeruginosa and is responsible for the production of virulence factors and biofilm formation. Thus, synthetic small molecules that can target the PqsR (MvfR) receptor can be utilized as quorum sensing inhibitors to treat P. aeruginosa infections. In this study, we report the synthesis of novel thioether-linked dihydropyrrol-2-one (DHP) analogues as PqsR antagonists. Compound 7g containing a 2-mercaptopyridyl linkage effectively inhibited the pqs system with an IC₅₀ of 32 µM in P. aeruginosa PAO1. Additionally, these inhibitors significantly reduced bacterial aggregation and biofilm formation without affecting planktonic growth. The molecular docking study suggest that these inhibitors bind with the ligand binding domain of the MvfR as a competitive antagonist.

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http://hdl.handle.net/10453/148095