Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

Suzie Park; Han Shin Kim; Kiwon Ok; Yunhye Kim; Hee Deung Park; Youngjoo Byun

doi:10.1016/j.bmcl.2015.05.054

Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

Suzie Park, Han Shin Kim, Kiwon Ok, Yunhye Kim, Hee Deung Park, Youngjoo Byun

School of Civil, Environmental and Architectural Engineering

Research output: Contribution to journal › Article › peer-review

31 Citations (Scopus)

Abstract

Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35-67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.

Original language	English
Pages (from-to)	2913-2917
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2015.05.054
Publication status	Published - 2015 Jun 11

Keywords

Biofilm inhibition
Pseudomonas aeruginosa
Pyrone
Quorum sensing

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2015.05.054

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title = "Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors",

abstract = "Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35-67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.",

keywords = "Biofilm inhibition, Pseudomonas aeruginosa, Pyrone, Quorum sensing",

author = "Suzie Park and Kim, {Han Shin} and Kiwon Ok and Yunhye Kim and Park, {Hee Deung} and Youngjoo Byun",

note = "Funding Information: We are grateful for the financial support from National Research Foundation of Korea ( 2012R1A1A2043292 to H.-D.P, 2014R1A1A2056522 and 2014R1A4A1007304 to Y.B). Publisher Copyright: {\textcopyright} 2015 Elsevier Ltd. All rights reserved.",

year = "2015",

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day = "11",

doi = "10.1016/j.bmcl.2015.05.054",

language = "English",

volume = "25",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Park, Suzie

AU - Kim, Han Shin

AU - Ok, Kiwon

AU - Kim, Yunhye

AU - Park, Hee Deung

AU - Byun, Youngjoo

N1 - Funding Information: We are grateful for the financial support from National Research Foundation of Korea ( 2012R1A1A2043292 to H.-D.P, 2014R1A1A2056522 and 2014R1A4A1007304 to Y.B). Publisher Copyright: © 2015 Elsevier Ltd. All rights reserved.

PY - 2015/6/11

Y1 - 2015/6/11

N2 - Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35-67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.

AB - Novel pyrone-derived quorum sensing (QS) ligands to inhibit the binding of OdDHL to the LasR of Pseudomonas aeruginosa were designed, synthesized and evaluated. Among the analogs, the most potent compound 8 exhibited strong in vitro inhibitory activities against biofilm formation and down-regulated OdDHL/LasR-associated genes by 35-67%. The binding mode of 8 in silico was highly similar to that of the crystal ligand OdDHL in the active site of LasR.

KW - Biofilm inhibition

KW - Pseudomonas aeruginosa

KW - Pyrone

KW - Quorum sensing

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U2 - 10.1016/j.bmcl.2015.05.054

DO - 10.1016/j.bmcl.2015.05.054

M3 - Article

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VL - 25

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EP - 2917

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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IS - 15

ER -

Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

Abstract

Keywords

ASJC Scopus subject areas

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