Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa
Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening...
| Main Authors: | , , , , , , , , , |
|---|---|
| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2017
|
| Subjects: | |
| Online Access: | https://hdl.handle.net/10356/85223 http://hdl.handle.net/10220/43675 |
| _version_ | 1826119657672671232 |
|---|---|
| author | Fong, July Yuan, Mingjun Jakobsen, Tim Holm Mortensen, Kim T. Delos Santos, May Margarette Salido Chua, Song Lin Yang, Liang Tan, Choon Hong Givskov, Michael Nielsen, Thomas Eiland |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Fong, July Yuan, Mingjun Jakobsen, Tim Holm Mortensen, Kim T. Delos Santos, May Margarette Salido Chua, Song Lin Yang, Liang Tan, Choon Hong Givskov, Michael Nielsen, Thomas Eiland |
| author_sort | Fong, July |
| collection | NTU |
| description | Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening of an in-house compound library revealed two sulfur-containing compounds which possess structural resemblance with ajoene and inhibit QS in bioreporter assay. Following a quantitative structure–activity relationship (SAR) study, 25 disulfide bond-containing analogues were synthesized and tested for QS inhibition activities. SAR study indicated that the allyl group could be replaced with other substituents, with the most active being benzothiazole derivative (IC50 = 0.56 μM). The compounds were able to reduce QS-regulated virulence factors (elastase, rhamnolipid, and pyocyanin) and successfully inhibit P. aeruginosa infection in murine model of implant-associated infection. Altogether, the QS inhibition activity of the synthesized compounds is encouraging for further exploration of novel analogues in antimicrobial drug development. |
| first_indexed | 2024-10-01T05:04:00Z |
| format | Journal Article |
| id | ntu-10356/85223 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:04:00Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/852232020-03-07T12:18:09Z Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa Fong, July Yuan, Mingjun Jakobsen, Tim Holm Mortensen, Kim T. Delos Santos, May Margarette Salido Chua, Song Lin Yang, Liang Tan, Choon Hong Givskov, Michael Nielsen, Thomas Eiland School of Biological Sciences School of Physical and Mathematical Sciences Singapore Centre for Environmental Life Sciences Engineering Disulfide Bond Ajoene Analogues Since its discovery 22 years ago, the bacterial cell-to-cell communication system, termed quorum sensing (QS), has shown potential as antipathogenic target. Previous studies reported that ajoene from garlic inhibits QS in opportunistic human pathogen Pseudomonas aeruginosa. In this study, screening of an in-house compound library revealed two sulfur-containing compounds which possess structural resemblance with ajoene and inhibit QS in bioreporter assay. Following a quantitative structure–activity relationship (SAR) study, 25 disulfide bond-containing analogues were synthesized and tested for QS inhibition activities. SAR study indicated that the allyl group could be replaced with other substituents, with the most active being benzothiazole derivative (IC50 = 0.56 μM). The compounds were able to reduce QS-regulated virulence factors (elastase, rhamnolipid, and pyocyanin) and successfully inhibit P. aeruginosa infection in murine model of implant-associated infection. Altogether, the QS inhibition activity of the synthesized compounds is encouraging for further exploration of novel analogues in antimicrobial drug development. MOE (Min. of Education, S’pore) NRF (Natl Research Foundation, S’pore) 2017-09-04T07:10:49Z 2019-12-06T15:59:49Z 2017-09-04T07:10:49Z 2019-12-06T15:59:49Z 2016 Journal Article Fong, J., Yuan, M., Jakobsen, T. H., Mortensen, K. T., Delos Santos, M. M. S., Chua, S. L., et al. (2017). Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa. Journal of Medicinal Chemistry, 60(1), 215-227. 0022-2623 https://hdl.handle.net/10356/85223 http://hdl.handle.net/10220/43675 10.1021/acs.jmedchem.6b01025 en Journal of Medicinal Chemistry © 2016 American Chemical Society. |
| spellingShingle | Disulfide Bond Ajoene Analogues Fong, July Yuan, Mingjun Jakobsen, Tim Holm Mortensen, Kim T. Delos Santos, May Margarette Salido Chua, Song Lin Yang, Liang Tan, Choon Hong Givskov, Michael Nielsen, Thomas Eiland Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of Pseudomonas aeruginosa |
| title | Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of
Pseudomonas aeruginosa |
| title_full | Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of
Pseudomonas aeruginosa |
| title_fullStr | Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of
Pseudomonas aeruginosa |
| title_full_unstemmed | Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of
Pseudomonas aeruginosa |
| title_short | Disulfide Bond-Containing Ajoene Analogues As Novel Quorum Sensing Inhibitors of
Pseudomonas aeruginosa |
| title_sort | disulfide bond containing ajoene analogues as novel quorum sensing inhibitors of pseudomonas aeruginosa |
| topic | Disulfide Bond Ajoene Analogues |
| url | https://hdl.handle.net/10356/85223 http://hdl.handle.net/10220/43675 |
| work_keys_str_mv | AT fongjuly disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT yuanmingjun disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT jakobsentimholm disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT mortensenkimt disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT delossantosmaymargarettesalido disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT chuasonglin disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT yangliang disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT tanchoonhong disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT givskovmichael disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa AT nielsenthomaseiland disulfidebondcontainingajoeneanaloguesasnovelquorumsensinginhibitorsofpseudomonasaeruginosa |