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

^*Corresponding author for this work

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

46 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

Bibliographical 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:
© 2015 Elsevier Ltd. All rights reserved.

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

Cite this

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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",

month = jun,

day = "11",

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

language = "English",

volume = "25",

pages = "2913--2917",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Design, synthesis and biological evaluation of 4-(alkyloxy)-6-methyl-2H-pyran-2-one derivatives as quorum sensing inhibitors

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

UR - https://www.scopus.com/pages/publications/84930924160

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DO - 10.1016/j.bmcl.2015.05.054

M3 - Article

C2 - 26048802

AN - SCOPUS:84930924160

SN - 0960-894X

VL - 25

SP - 2913

EP - 2917

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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