Sökning: onr:"swepub:oai:DiVA.org:uu-414283" >
Hit Identification ...
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Soukarieh, FadiUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.;Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.
(författare)
Hit Identification of New Potent PqsR Antagonists as Inhibitors of Quorum Sensing in Planktonic and Biofilm Grown Pseudomonas aeruginosa
- Artikel/kapitelEngelska2020
Förlag, utgivningsår, omfång ...
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2020-05-04
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FRONTIERS MEDIA SA,2020
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-414283
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-414283URI
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https://doi.org/10.3389/fchem.2020.00204DOI
Kompletterande språkuppgifter
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Språk:engelska
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Sammanfattning på:engelska
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Klassifikation
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
Anmärkningar
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Current treatments for Pseudomonas aeruginosa infections are becoming less effective because of the increasing rates of multi-antibiotic resistance. Pharmacological targeting of virulence through inhibition of quorum sensing (QS) dependent virulence gene regulation has considerable therapeutic potential. In P. aeruginosa, the pqs QS system regulates the production of multiple virulence factors as well as biofilm maturation and is a promising approach for developing antimicrobial adjuvants for combatting drug resistance. In this work, we report the hit optimisation for a series of potent novel inhibitors of PqsR, a key regulator of the pqs system, bearing a 2-((5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)thio) acetamide scaffold. The initial hit compound 7 (PAO1-L IC50 0.98 +/- 0.02 mu M, PA14 inactive at 10 mu M) was obtained through a virtual screening campaign performed on the PqsR ligand binding domain using the University of Nottingham Managed Chemical Compound Collection. Hit optimisation gave compounds with enhanced potency against strains PAO1-L and PA14, evaluated using P. aeruginosa pqs-based QS bioreporter assays. Compound 40 (PAO1-L IC50 0.25 +/- 0.12 mu M, PA14 IC50 0.34 +/- 0.03 mu M) is one of the most potent PqsR antagonists reported showing significant inhibition of P. aeruginosa pyocyanin production and pqs system signaling in both planktonic cultures and biofilms. The co-crystal structure of 40 with the PqsR ligand binding domain revealed the specific binding interactions occurring between inhibitor and this key regulatory protein.
Ämnesord och genrebeteckningar
Biuppslag (personer, institutioner, konferenser, titlar ...)
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Liu, RuilingUniv Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(författare)
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Romero, ManuelUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.;Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.
(författare)
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Roberston, Shaun N.Univ Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.;Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.
(författare)
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Richardson, WilliamUniv Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(författare)
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Lucanto, SimoneUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.;Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.
(författare)
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Oton, Eduard VicoUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.
(författare)
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Qudus, Naim RuhulUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.
(författare)
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Mashabi, AlaaUniv Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(författare)
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Grossman, ScottUniv Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(författare)
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Ali, SadiqurUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.
(författare)
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Sou, TomásUppsala universitet,Institutionen för farmaci,Institutionen för farmaceutisk biovetenskap(Swepub:uu)tomso488
(författare)
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Kukavica-Ibrulj, IrenaUniv Laval, Inst Biol Integrat & Syst, Quebec City, PQ, Canada.
(författare)
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Levesque, Roger C.Univ Laval, Inst Biol Integrat & Syst, Quebec City, PQ, Canada.
(författare)
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Bergström, Christel,1973-Uppsala universitet,Institutionen för farmaci(Swepub:uu)cjo29958
(författare)
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Halliday, NigelUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.
(författare)
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Mistry, Shailesh N.Univ Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(författare)
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Emsley, JonasUniv Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.;Univ Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(författare)
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Heeb, StephanUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.
(författare)
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Williams, PaulUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.;Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.
(författare)
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Camara, MiguelUniv Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.;Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.
(författare)
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Stocks, Michael J.Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.;Univ Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(författare)
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Univ Nottingham, Biodiscovery Inst, Sch Life Sci, Nottingham, England.;Univ Nottingham, Natl Biofilms Innovat Ctr, Nottingham, England.Univ Nottingham, Biodiscovery Inst, Sch Pharm, Nottingham, England.
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Frontiers in Chemistry: FRONTIERS MEDIA SA82296-2646
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Soukarieh, Fadi
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Liu, Ruiling
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Romero, Manuel
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Roberston, Shaun ...
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Richardson, Will ...
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Lucanto, Simone
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visa fler...
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Oton, Eduard Vic ...
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Qudus, Naim Ruhu ...
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Mashabi, Alaa
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Grossman, Scott
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Ali, Sadiqur
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Sou, Tomás
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Kukavica-Ibrulj, ...
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Levesque, Roger ...
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Bergström, Chris ...
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Halliday, Nigel
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Mistry, Shailesh ...
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Emsley, Jonas
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Heeb, Stephan
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Williams, Paul
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Camara, Miguel
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Stocks, Michael ...
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