Dihydropyrrolones as bacterial quorum sensing inhibitors

Bacteria regulate their pathogenicity and biofilm formation through quorum sensing (QS), which is an intercellular communication system mediated by the binding of signaling molecules to QS receptors such as LasR. In this study, a range of dihydropyrrolone (DHP) analogues were synthesized via the lac...

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Main Authors: Almohaywi, Basmah, Yu, Tsz Tin, Iskander, George, Chan, Daniel S. H., Ho, Kitty K. K., Rice, Scott A., Black, David StC., Griffith, Renate, Kumar, Naresh
Other Authors: Singapore Centre for Environmental Life Sciences and Engineering
Format: Article
Language:English
Published: 2020
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Online Access:https://hdl.handle.net/10356/144458
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1444582020-11-06T05:01:25Z Dihydropyrrolones as bacterial quorum sensing inhibitors Almohaywi, Basmah Yu, Tsz Tin Iskander, George Chan, Daniel S. H. Ho, Kitty K. K. Rice, Scott A. Black, David StC. Griffith, Renate Kumar, Naresh Singapore Centre for Environmental Life Sciences and Engineering Science::Biological sciences Quorum Sensing Biofilm Inhibition Bacteria regulate their pathogenicity and biofilm formation through quorum sensing (QS), which is an intercellular communication system mediated by the binding of signaling molecules to QS receptors such as LasR. In this study, a range of dihydropyrrolone (DHP) analogues were synthesized via the lactone-lactam conversion of lactone intermediates. The synthesized compounds were tested for their ability to inhibit QS, biofilm formation and bacterial growth of Pseudomonas aeruginosa. The compounds were also docked into a LasR crystal structure to rationalize the observed structure-activity relationships. The most active compound identified in this study was compound 9i, which showed 63.1% QS inhibition of at 31.25 µM and 60% biofilm reduction at 250 µM with only moderate toxicity towards bacterial cell growth. This work was supported by a linkage project grant from the Australian Research Council (LP150100752). We thank the NMR and Bioanalytical Mass Spectrometry Facility (BMSF) facilities at UNSW. The authors would like to acknowledge the Saudi Ministry of Education and King Khalid University for an Endowment Fund and financial support given to B. Almohaywi. 2020-11-06T02:50:27Z 2020-11-06T02:50:27Z 2019 Journal Article Almohaywi, B., Yu, T. T., Iskander, G., Chan, D. S. H., Ho, K. K. K., Rice, S. A., . . . Kumar N. (2019). Dihydropyrrolones as bacterial quorum sensing inhibitors. Bioorganic and Medicinal Chemistry Letters, 29(9), 1054-1059. doi:10.1016/j.bmcl.2019.03.004 0960-894X https://hdl.handle.net/10356/144458 10.1016/j.bmcl.2019.03.004 30857746 9 29 1054 1059 en Bioorganic and Medicinal Chemistry Letters © 2019 Elsevier Ltd. All rights reserved.
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic Science::Biological sciences
Quorum Sensing
Biofilm Inhibition
spellingShingle Science::Biological sciences
Quorum Sensing
Biofilm Inhibition
Almohaywi, Basmah
Yu, Tsz Tin
Iskander, George
Chan, Daniel S. H.
Ho, Kitty K. K.
Rice, Scott A.
Black, David StC.
Griffith, Renate
Kumar, Naresh
Dihydropyrrolones as bacterial quorum sensing inhibitors
description Bacteria regulate their pathogenicity and biofilm formation through quorum sensing (QS), which is an intercellular communication system mediated by the binding of signaling molecules to QS receptors such as LasR. In this study, a range of dihydropyrrolone (DHP) analogues were synthesized via the lactone-lactam conversion of lactone intermediates. The synthesized compounds were tested for their ability to inhibit QS, biofilm formation and bacterial growth of Pseudomonas aeruginosa. The compounds were also docked into a LasR crystal structure to rationalize the observed structure-activity relationships. The most active compound identified in this study was compound 9i, which showed 63.1% QS inhibition of at 31.25 µM and 60% biofilm reduction at 250 µM with only moderate toxicity towards bacterial cell growth.
author2 Singapore Centre for Environmental Life Sciences and Engineering
author_facet Singapore Centre for Environmental Life Sciences and Engineering
Almohaywi, Basmah
Yu, Tsz Tin
Iskander, George
Chan, Daniel S. H.
Ho, Kitty K. K.
Rice, Scott A.
Black, David StC.
Griffith, Renate
Kumar, Naresh
format Article
author Almohaywi, Basmah
Yu, Tsz Tin
Iskander, George
Chan, Daniel S. H.
Ho, Kitty K. K.
Rice, Scott A.
Black, David StC.
Griffith, Renate
Kumar, Naresh
author_sort Almohaywi, Basmah
title Dihydropyrrolones as bacterial quorum sensing inhibitors
title_short Dihydropyrrolones as bacterial quorum sensing inhibitors
title_full Dihydropyrrolones as bacterial quorum sensing inhibitors
title_fullStr Dihydropyrrolones as bacterial quorum sensing inhibitors
title_full_unstemmed Dihydropyrrolones as bacterial quorum sensing inhibitors
title_sort dihydropyrrolones as bacterial quorum sensing inhibitors
publishDate 2020
url https://hdl.handle.net/10356/144458
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