Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-Butyramide
Quorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-<i>N</i>-(2′-phenylethyl)-butyramide, produced by a marine bacterium identified as <i>Halobacillus&...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-07-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/17/7/389 |
| _version_ | 1811301666658451456 |
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| author | Susan M. Meschwitz Margaret E. Teasdale Ann Mozzer Nicole Martin Jiayuan Liu Stephanie Forschner-Dancause David C. Rowley |
| author_facet | Susan M. Meschwitz Margaret E. Teasdale Ann Mozzer Nicole Martin Jiayuan Liu Stephanie Forschner-Dancause David C. Rowley |
| author_sort | Susan M. Meschwitz |
| collection | DOAJ |
| description | Quorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-<i>N</i>-(2′-phenylethyl)-butyramide, produced by a marine bacterium identified as <i>Halobacillus</i> <i>salinus</i>, inhibits QS controlled phenotypes in multiple Gram-negative reporter strains. Here we report that <i>N</i>-phenethyl hexanamide, a structurally-related compound produced by the marine bacterium <i>Vibrio</i> <i>neptunius</i>, similarly demonstrates QS inhibitory properties. To more fully explore structure−activity relationships within this new class of QS inhibitors, a panel of twenty analogs was synthesized and biologically evaluated. Several compounds were identified with increased attenuation of QS-regulated phenotypes, most notably <i>N</i>-(4-fluorophenyl)-3-phenylpropanamide against the marine pathogen <i>Vibrio harveyi</i> (IC<sub>50</sub> = 1.1 µM). These findings support the opportunity to further develop substituted phenethylamides as QS inhibitors. |
| first_indexed | 2024-04-13T07:12:57Z |
| format | Article |
| id | doaj.art-eeb23e7d45ff4508930a7c642497f7d3 |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-13T07:12:57Z |
| publishDate | 2019-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-eeb23e7d45ff4508930a7c642497f7d32022-12-22T02:56:50ZengMDPI AGMarine Drugs1660-33972019-07-0117738910.3390/md17070389md17070389Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-ButyramideSusan M. Meschwitz0Margaret E. Teasdale1Ann Mozzer2Nicole Martin3Jiayuan Liu4Stephanie Forschner-Dancause5David C. Rowley6Department of Chemistry, Salve Regina University, Newport, RI 02840, USADepartment of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USADepartment of Chemistry, Salve Regina University, Newport, RI 02840, USADepartment of Chemistry, Salve Regina University, Newport, RI 02840, USADepartment of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USADepartment of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USADepartment of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USAQuorum sensing (QS) antagonists have been proposed as novel therapeutic agents to combat bacterial infections. We previously reported that the secondary metabolite 3-methyl-<i>N</i>-(2′-phenylethyl)-butyramide, produced by a marine bacterium identified as <i>Halobacillus</i> <i>salinus</i>, inhibits QS controlled phenotypes in multiple Gram-negative reporter strains. Here we report that <i>N</i>-phenethyl hexanamide, a structurally-related compound produced by the marine bacterium <i>Vibrio</i> <i>neptunius</i>, similarly demonstrates QS inhibitory properties. To more fully explore structure−activity relationships within this new class of QS inhibitors, a panel of twenty analogs was synthesized and biologically evaluated. Several compounds were identified with increased attenuation of QS-regulated phenotypes, most notably <i>N</i>-(4-fluorophenyl)-3-phenylpropanamide against the marine pathogen <i>Vibrio harveyi</i> (IC<sub>50</sub> = 1.1 µM). These findings support the opportunity to further develop substituted phenethylamides as QS inhibitors.https://www.mdpi.com/1660-3397/17/7/389quorum sensing<i>Vibrio</i>phenethylamide |
| spellingShingle | Susan M. Meschwitz Margaret E. Teasdale Ann Mozzer Nicole Martin Jiayuan Liu Stephanie Forschner-Dancause David C. Rowley Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-Butyramide Marine Drugs quorum sensing <i>Vibrio</i> phenethylamide |
| title | Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-Butyramide |
| title_full | Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-Butyramide |
| title_fullStr | Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-Butyramide |
| title_full_unstemmed | Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-Butyramide |
| title_short | Antagonism of Quorum Sensing Phenotypes by Analogs of the Marine Bacterial Secondary Metabolite 3-Methyl-<i>N</i>-(2′-Phenylethyl)-Butyramide |
| title_sort | antagonism of quorum sensing phenotypes by analogs of the marine bacterial secondary metabolite 3 methyl i n i 2 phenylethyl butyramide |
| topic | quorum sensing <i>Vibrio</i> phenethylamide |
| url | https://www.mdpi.com/1660-3397/17/7/389 |
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