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Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

Selectively methylated analogues of naturally occurring 2-heptyl-4(1H)-quinolones, which are alkaloids common within the Rutaceae family and moreover are associated with quorum sensing and virulence of the human pathogen Pseudomonas aeruginosa, have been prepared. While the synthesis by direct methy...

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Autores principales: Thierbach, Sven, Wienhold, Max, Fetzner, Susanne, Hennecke, Ulrich
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Beilstein-Institut 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350858/
https://www.ncbi.nlm.nih.gov/pubmed/30745993
http://dx.doi.org/10.3762/bjoc.15.18
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author Thierbach, Sven
Wienhold, Max
Fetzner, Susanne
Hennecke, Ulrich
author_facet Thierbach, Sven
Wienhold, Max
Fetzner, Susanne
Hennecke, Ulrich
author_sort Thierbach, Sven
collection PubMed
description Selectively methylated analogues of naturally occurring 2-heptyl-4(1H)-quinolones, which are alkaloids common within the Rutaceae family and moreover are associated with quorum sensing and virulence of the human pathogen Pseudomonas aeruginosa, have been prepared. While the synthesis by direct methylation was successful for 3-unsubstituted 2-heptyl-4(1H)-quinolones, methylated derivatives of the Pseudomonas quinolone signal (PQS) were synthesized from 3-iodinated quinolones by methylation and iodine–metal exchange/oxidation. The two N- and O-methylated derivatives of the PQS showed strong quorum sensing activity comparable to that of PQS itself. Staphylococcus aureus, another pathogenic bacterium often co-occurring with P. aeruginosa especially in the lung of cystic fibrosis patients, was inhibited in planktonic growth and cellular respiration by the 4-O-methylated derivatives of HQNO and HHQ, respectively.
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spelling pubmed-63508582019-02-11 Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS Thierbach, Sven Wienhold, Max Fetzner, Susanne Hennecke, Ulrich Beilstein J Org Chem Full Research Paper Selectively methylated analogues of naturally occurring 2-heptyl-4(1H)-quinolones, which are alkaloids common within the Rutaceae family and moreover are associated with quorum sensing and virulence of the human pathogen Pseudomonas aeruginosa, have been prepared. While the synthesis by direct methylation was successful for 3-unsubstituted 2-heptyl-4(1H)-quinolones, methylated derivatives of the Pseudomonas quinolone signal (PQS) were synthesized from 3-iodinated quinolones by methylation and iodine–metal exchange/oxidation. The two N- and O-methylated derivatives of the PQS showed strong quorum sensing activity comparable to that of PQS itself. Staphylococcus aureus, another pathogenic bacterium often co-occurring with P. aeruginosa especially in the lung of cystic fibrosis patients, was inhibited in planktonic growth and cellular respiration by the 4-O-methylated derivatives of HQNO and HHQ, respectively. Beilstein-Institut 2019-01-21 /pmc/articles/PMC6350858/ /pubmed/30745993 http://dx.doi.org/10.3762/bjoc.15.18 Text en Copyright © 2019, Thierbach et al. https://creativecommons.org/licenses/by/4.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0). Please note that the reuse, redistribution and reproduction in particular requires that the authors and source are credited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms)
spellingShingle Full Research Paper
Thierbach, Sven
Wienhold, Max
Fetzner, Susanne
Hennecke, Ulrich
Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
title Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
title_full Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
title_fullStr Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
title_full_unstemmed Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
title_short Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS
title_sort synthesis and biological activity of methylated derivatives of the pseudomonas metabolites hhq, hqno and pqs
topic Full Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6350858/
https://www.ncbi.nlm.nih.gov/pubmed/30745993
http://dx.doi.org/10.3762/bjoc.15.18
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