Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors
Bacterial infections, particularly hospital-acquired infections caused by Pseudomonas aeruginosa, have become a global threat with a high mortality rate. Gram-negative bacteria including P. aeruginosa employ N-acyl homoserine lactones (AHLs) as chemical signals to regulate the expression of pathogen...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2018
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| Online Access: | https://hdl.handle.net/10356/84293 http://hdl.handle.net/10220/45109 |
| _version_ | 1826111546244202496 |
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| author | Almohaywi, Basmah Taunk, Aditi Nizalapur, Shashidhar Iskander, George Griffith, Renate Kumar, Naresh Wenholz, Daniel S. Biswas, Nripendra N. Ho, Kitty K. K. Rice, Scott A. Black, David StC. |
| author2 | Singapore Centre for Environmental Life Sciences Engineering |
| author_facet | Singapore Centre for Environmental Life Sciences Engineering Almohaywi, Basmah Taunk, Aditi Nizalapur, Shashidhar Iskander, George Griffith, Renate Kumar, Naresh Wenholz, Daniel S. Biswas, Nripendra N. Ho, Kitty K. K. Rice, Scott A. Black, David StC. |
| author_sort | Almohaywi, Basmah |
| collection | NTU |
| description | Bacterial infections, particularly hospital-acquired infections caused by Pseudomonas aeruginosa, have become a global threat with a high mortality rate. Gram-negative bacteria including P. aeruginosa employ N-acyl homoserine lactones (AHLs) as chemical signals to regulate the expression of pathogenic phenotypes through a mechanism called quorum sensing (QS). Recently, strategies targeting bacterial behaviour or QS have received great attention due to their ability to disarm rather than kill pathogenic bacteria, which lowers the evolutionary burden on bacteria and the risk of resistance development. In the present study, we report the design and synthesis of N-alkyl- and N-aryl 3,4 dichloro- and 3,4-dibromopyrrole-2-one derivatives through the reductive amination of mucochloric and mucobromic acid with aliphatic and aromatic amines. The quorum sensing inhibition (QSI) activity of the synthesized compounds was determined against a P. aeruginosa MH602 reporter strain. The phenolic compounds exhibited the best activity with 80% and 75% QSI at 250 µM and were comparable in activity to the positive control compound Fu-30. Computational docking studies performed using the LasR receptor protein of P. aeruginosa suggested the importance of hydrogen bonding and hydrophobic interactions for QSI. |
| first_indexed | 2024-10-01T02:52:30Z |
| format | Journal Article |
| id | ntu-10356/84293 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:52:30Z |
| publishDate | 2018 |
| record_format | dspace |
| spelling | ntu-10356/842932020-09-21T11:32:02Z Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors Almohaywi, Basmah Taunk, Aditi Nizalapur, Shashidhar Iskander, George Griffith, Renate Kumar, Naresh Wenholz, Daniel S. Biswas, Nripendra N. Ho, Kitty K. K. Rice, Scott A. Black, David StC. Singapore Centre for Environmental Life Sciences Engineering Quorum Sensing Pseudomonas Aeruginosa Bacterial infections, particularly hospital-acquired infections caused by Pseudomonas aeruginosa, have become a global threat with a high mortality rate. Gram-negative bacteria including P. aeruginosa employ N-acyl homoserine lactones (AHLs) as chemical signals to regulate the expression of pathogenic phenotypes through a mechanism called quorum sensing (QS). Recently, strategies targeting bacterial behaviour or QS have received great attention due to their ability to disarm rather than kill pathogenic bacteria, which lowers the evolutionary burden on bacteria and the risk of resistance development. In the present study, we report the design and synthesis of N-alkyl- and N-aryl 3,4 dichloro- and 3,4-dibromopyrrole-2-one derivatives through the reductive amination of mucochloric and mucobromic acid with aliphatic and aromatic amines. The quorum sensing inhibition (QSI) activity of the synthesized compounds was determined against a P. aeruginosa MH602 reporter strain. The phenolic compounds exhibited the best activity with 80% and 75% QSI at 250 µM and were comparable in activity to the positive control compound Fu-30. Computational docking studies performed using the LasR receptor protein of P. aeruginosa suggested the importance of hydrogen bonding and hydrophobic interactions for QSI. Published version 2018-07-18T08:26:20Z 2019-12-06T15:42:15Z 2018-07-18T08:26:20Z 2019-12-06T15:42:15Z 2018 Journal Article Almohaywi, B., Taunk, A., Wenholz, D. S., Nizalapur, S., Biswas, N. N., Ho, K. K. K., et al. (2018). Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors. Molecules, 23(5), 1106-. 1420-3049 https://hdl.handle.net/10356/84293 http://hdl.handle.net/10220/45109 10.3390/molecules23051106 en Molecules © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). 29 p. application/pdf |
| spellingShingle | Quorum Sensing Pseudomonas Aeruginosa Almohaywi, Basmah Taunk, Aditi Nizalapur, Shashidhar Iskander, George Griffith, Renate Kumar, Naresh Wenholz, Daniel S. Biswas, Nripendra N. Ho, Kitty K. K. Rice, Scott A. Black, David StC. Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors |
| title | Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors |
| title_full | Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors |
| title_fullStr | Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors |
| title_full_unstemmed | Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors |
| title_short | Design and Synthesis of Lactams Derived from Mucochloric and Mucobromic Acids as Pseudomonas aeruginosa Quorum Sensing Inhibitors |
| title_sort | design and synthesis of lactams derived from mucochloric and mucobromic acids as pseudomonas aeruginosa quorum sensing inhibitors |
| topic | Quorum Sensing Pseudomonas Aeruginosa |
| url | https://hdl.handle.net/10356/84293 http://hdl.handle.net/10220/45109 |
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