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.
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 339-700, South Korea.
authors.forename: Suzie
authors.initials: S
authors.lastname: Park
authors.affiliation: School of Civil, Environmental and Architectural Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, South Korea.
authors.forename: Han-Shin
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 339-700, South Korea.
authors.forename: Kiwon
authors.initials: K
authors.lastname: Ok
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 339-700, South Korea.
authors.forename: YunHye
authors.initials: Y
authors.lastname: Kim
authors.affiliation: School of Civil, Environmental and Architectural Engineering, Korea University, Anam-Dong, Seongbuk-Gu, Seoul 136-713, South Korea. Electronic address: heedeung@korea.ac.kr.
authors.forename: Hee-Deung
authors.initials: HD
authors.lastname: Park
authors.affiliation: College of Pharmacy, Korea University, 2511 Sejong-ro, Jochiwon-eup, Sejong 339-700, South Korea; Biomedical Research Center, Korea University Guro Hospital, 148 Gurodong-ro, Guro-gu, Seoul 152-703, South Korea. Electronic address: yjbyun1@korea.ac.kr.
authors.forename: Youngjoo
authors.initials: Y
authors.lastname: Byun
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000378:metabolism*; D018441:Biofilms / Q000187:drug effects*; D006714:Homoserine / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D062105:Molecular Docking Simulation; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology / Q000517:prevention & control; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D053038:Quorum Sensing / Q000187:drug effects*; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; C080365:LasR protein, Pseudomonas aeruginosa; C109860:N-(3-oxododecanoyl)homoserine lactone; D011753:Pyrones; D015534:Trans-Activators; D006714:Homoserine; D015107:4-Butyrolactone
keywords: Biofilm inhibition; Pseudomonas aeruginosa; Pyrone; Quorum sensing