Natural Product Rottlerin Derivatives Targeting Quorum Sensing
Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of <i>Pseudomonas aeruginosa.&l...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/12/3745 |
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| author | Dittu Suresh Shekh Sabir Tsz Tin Yu Daniel Wenholz Theerthankar Das David StC. Black Naresh Kumar |
| author_facet | Dittu Suresh Shekh Sabir Tsz Tin Yu Daniel Wenholz Theerthankar Das David StC. Black Naresh Kumar |
| author_sort | Dittu Suresh |
| collection | DOAJ |
| description | Rottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of <i>Pseudomonas aeruginosa.</i> Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, <b>8b</b> and <b>8d</b>, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin. |
| first_indexed | 2024-03-10T10:15:13Z |
| format | Article |
| id | doaj.art-0e22734d31c3472289f970c1e404f2d1 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T10:15:13Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-0e22734d31c3472289f970c1e404f2d12023-11-22T00:51:03ZengMDPI AGMolecules1420-30492021-06-012612374510.3390/molecules26123745Natural Product Rottlerin Derivatives Targeting Quorum SensingDittu Suresh0Shekh Sabir1Tsz Tin Yu2Daniel Wenholz3Theerthankar Das4David StC. Black5Naresh Kumar6School of Chemistry, The University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Chemistry, The University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Chemistry, The University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Chemistry, The University of New South Wales, Sydney, NSW 2052, AustraliaDepartment of Infectious Diseases and Immunology, School of Medical Sciences, The University of Sydney, Sydney, NSW 2006, AustraliaSchool of Chemistry, The University of New South Wales, Sydney, NSW 2052, AustraliaSchool of Chemistry, The University of New South Wales, Sydney, NSW 2052, AustraliaRottlerin is a natural product consisting of chalcone and flavonoid scaffolds, both of which have previously shown quorum sensing (QS) inhibition in various bacteria. Therefore, the unique rottlerin scaffold highlights great potential in inhibiting the QS system of <i>Pseudomonas aeruginosa.</i> Rottlerin analogues were synthesised by modifications at its chalcone- and methylene-bridged acetophenone moieties. The synthesis of analogues was achieved using an established five-step synthetic strategy for chalcone derivatives and utilising the Mannich reaction at C6 of the chromene to construct morpholine analogues. Several pyranochromene chalcone derivatives were also generated using aldol conditions. All the synthetic rottlerin derivatives were screened for QS inhibition and growth inhibition against the related LasR QS system. The pyranochromene chalcone structures displayed high QS inhibitory activity with the most potent compounds, <b>8b</b> and <b>8d</b>, achieving QS inhibition of 49.4% and 40.6% and no effect on bacterial growth inhibition at 31 µM, respectively. Both compounds also displayed moderate biofilm inhibitory activity and reduced the production of pyocyanin.https://www.mdpi.com/1420-3049/26/12/3745natural productsrottlerinpyranochromene chalconequorum sensing inhibitors<i>Pseudomonas aeruginosa</i> |
| spellingShingle | Dittu Suresh Shekh Sabir Tsz Tin Yu Daniel Wenholz Theerthankar Das David StC. Black Naresh Kumar Natural Product Rottlerin Derivatives Targeting Quorum Sensing Molecules natural products rottlerin pyranochromene chalcone quorum sensing inhibitors <i>Pseudomonas aeruginosa</i> |
| title | Natural Product Rottlerin Derivatives Targeting Quorum Sensing |
| title_full | Natural Product Rottlerin Derivatives Targeting Quorum Sensing |
| title_fullStr | Natural Product Rottlerin Derivatives Targeting Quorum Sensing |
| title_full_unstemmed | Natural Product Rottlerin Derivatives Targeting Quorum Sensing |
| title_short | Natural Product Rottlerin Derivatives Targeting Quorum Sensing |
| title_sort | natural product rottlerin derivatives targeting quorum sensing |
| topic | natural products rottlerin pyranochromene chalcone quorum sensing inhibitors <i>Pseudomonas aeruginosa</i> |
| url | https://www.mdpi.com/1420-3049/26/12/3745 |
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