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Synthesis of Alkyne-Substituted Dihydropyrrolones as Bacterial Quorum-Sensing Inhibitors of Pseudomonas aeruginosa
The Quorum-sensing system in is responsible for the pathogenicity and the production of virulence factors and biofilm formation. Dihydropyrrolones were previously found to act as inhibitors of QS-dependent bacterial phenotypes. In this study, a range of dihydropyrrolone (DHP) analogues was synthesiz...
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| Published in: | Antibiotics (Basel) 2022-01, Vol.11 (2), p.151 |
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| Main Authors: | , , , , , , |
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| cited_by | cdi_FETCH-LOGICAL-c499t-6a568b47dde556bfb4a3e685bb8eb635a2c15cfdc633327b4c2281445a2494743 |
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| cites | cdi_FETCH-LOGICAL-c499t-6a568b47dde556bfb4a3e685bb8eb635a2c15cfdc633327b4c2281445a2494743 |
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| container_issue | 2 |
| container_start_page | 151 |
| container_title | Antibiotics (Basel) |
| container_volume | 11 |
| creator | Almohaywi, Basmah Yu, Tsz Tin Iskander, George Sabir, Shekh Bhadbhade, Mohan Black, David StC Kumar, Naresh |
| description | The Quorum-sensing system in
is responsible for the pathogenicity and the production of virulence factors and biofilm formation. Dihydropyrrolones were previously found to act as inhibitors of QS-dependent bacterial phenotypes. In this study, a range of dihydropyrrolone (DHP) analogues was synthesized via the lactone-lactam conversion of lactone intermediates followed by the formation of novel acetylene analogues of dihydropyrrolones from brominated dihydropyrrolones via Sonogashira coupling reactions in moderate to high yields. Upon biological testing, the most potent compounds,
-
and
showed higher bacterial quorum-sensing inhibitory (QSI) activity against
reporter strain at 62.5 µM. Structure-activity relationship studies revealed that di-alkynyl substituent at the exocyclic position of DHPs possessed higher QSI activities than those of mono-alkynyl DHPs. Moreover, a hexyl-substituent at C3 of DHPs was beneficial to QSI activity while a phenyl substituent at C4 of DHPs was detrimental to QSI activity of analogues. |
| doi_str_mv | 10.3390/antibiotics11020151 |
| format | article |
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is responsible for the pathogenicity and the production of virulence factors and biofilm formation. Dihydropyrrolones were previously found to act as inhibitors of QS-dependent bacterial phenotypes. In this study, a range of dihydropyrrolone (DHP) analogues was synthesized via the lactone-lactam conversion of lactone intermediates followed by the formation of novel acetylene analogues of dihydropyrrolones from brominated dihydropyrrolones via Sonogashira coupling reactions in moderate to high yields. Upon biological testing, the most potent compounds,
-
and
showed higher bacterial quorum-sensing inhibitory (QSI) activity against
reporter strain at 62.5 µM. Structure-activity relationship studies revealed that di-alkynyl substituent at the exocyclic position of DHPs possessed higher QSI activities than those of mono-alkynyl DHPs. Moreover, a hexyl-substituent at C3 of DHPs was beneficial to QSI activity while a phenyl substituent at C4 of DHPs was detrimental to QSI activity of analogues.</description><identifier>ISSN: 2079-6382</identifier><identifier>EISSN: 2079-6382</identifier><identifier>DOI: 10.3390/antibiotics11020151</identifier><identifier>PMID: 35203755</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acetylene ; alkyne synthesis ; Alkynes ; Amides ; Antibiotics ; Antimicrobial agents ; Bacteria ; Biofilms ; Bromination ; Carbon ; Chemical reactions ; dihydropyrrolones ; Drug resistance ; Inhibitors ; Intermediates ; Palladium ; Pathogenicity ; Pathogens ; Pharmaceutical sciences ; Phenotypes ; Pseudomonas aeruginosa ; quorum sensing ; Solvents ; Virulence ; Virulence factors</subject><ispartof>Antibiotics (Basel), 2022-01, Vol.11 (2), p.151</ispartof><rights>2022 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 (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 by the authors. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-6a568b47dde556bfb4a3e685bb8eb635a2c15cfdc633327b4c2281445a2494743</citedby><cites>FETCH-LOGICAL-c499t-6a568b47dde556bfb4a3e685bb8eb635a2c15cfdc633327b4c2281445a2494743</cites><orcidid>0000-0002-8484-7342 ; 0000-0002-3962-3040 ; 0000-0002-0951-9621 ; 0000-0001-9300-4737 ; 0000-0001-6389-3051</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2632192848/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2632192848?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,25732,27903,27904,36991,36992,44569,53769,53771,74872</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35203755$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Almohaywi, Basmah</creatorcontrib><creatorcontrib>Yu, Tsz Tin</creatorcontrib><creatorcontrib>Iskander, George</creatorcontrib><creatorcontrib>Sabir, Shekh</creatorcontrib><creatorcontrib>Bhadbhade, Mohan</creatorcontrib><creatorcontrib>Black, David StC</creatorcontrib><creatorcontrib>Kumar, Naresh</creatorcontrib><title>Synthesis of Alkyne-Substituted Dihydropyrrolones as Bacterial Quorum-Sensing Inhibitors of Pseudomonas aeruginosa</title><title>Antibiotics (Basel)</title><addtitle>Antibiotics (Basel)</addtitle><description>The Quorum-sensing system in
is responsible for the pathogenicity and the production of virulence factors and biofilm formation. Dihydropyrrolones were previously found to act as inhibitors of QS-dependent bacterial phenotypes. In this study, a range of dihydropyrrolone (DHP) analogues was synthesized via the lactone-lactam conversion of lactone intermediates followed by the formation of novel acetylene analogues of dihydropyrrolones from brominated dihydropyrrolones via Sonogashira coupling reactions in moderate to high yields. Upon biological testing, the most potent compounds,
-
and
showed higher bacterial quorum-sensing inhibitory (QSI) activity against
reporter strain at 62.5 µM. Structure-activity relationship studies revealed that di-alkynyl substituent at the exocyclic position of DHPs possessed higher QSI activities than those of mono-alkynyl DHPs. Moreover, a hexyl-substituent at C3 of DHPs was beneficial to QSI activity while a phenyl substituent at C4 of DHPs was detrimental to QSI activity of analogues.</description><subject>Acetylene</subject><subject>alkyne synthesis</subject><subject>Alkynes</subject><subject>Amides</subject><subject>Antibiotics</subject><subject>Antimicrobial agents</subject><subject>Bacteria</subject><subject>Biofilms</subject><subject>Bromination</subject><subject>Carbon</subject><subject>Chemical reactions</subject><subject>dihydropyrrolones</subject><subject>Drug resistance</subject><subject>Inhibitors</subject><subject>Intermediates</subject><subject>Palladium</subject><subject>Pathogenicity</subject><subject>Pathogens</subject><subject>Pharmaceutical sciences</subject><subject>Phenotypes</subject><subject>Pseudomonas aeruginosa</subject><subject>quorum sensing</subject><subject>Solvents</subject><subject>Virulence</subject><subject>Virulence factors</subject><issn>2079-6382</issn><issn>2079-6382</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNptkttqFEEQhgdRTIh5AkEGvPFmtM_TcyPEeFoIqKxeN93TNbu9znavfRDm7e1kY0jEvqmm6q-PquJvmucYvaZ0QG-0z864kN2YMEYEYY4fNacE9UMnqCSP7_1PmvOUdqi-AVOJ5NPmhHKCaM_5aRPXi89bSC61YWov5p-Lh25dTMoulwy2fe-2i43hsMQY5uAhtTq17_SYITo9t99KiGXfrcEn5zftym_rWDnEG9zXBMWGffC1RUMsG-dD0s-aJ5OeE5zfxrPmx8cP3y8_d1dfPq0uL666kQ1D7oTmQhrWWwucCzMZpikIyY2RYATlmoyYj5MdBaWU9IaNhEjMWC2wgfWMnjWrI9cGvVOH6PY6Lipop24SIW6UjvWAM6gJMzSIwVrKBQM8GYo0AZhqklhBdWW9PbIOxezBjuBz1PMD6MOKd1u1Cb-VlEKSnlTAq1tADL8KpKz2Lo0wz9pDKEmRuoXse0Fwlb78R7oLJfp6qmsVwQORTFYVParGGFKKMN0Ng5G6toj6j0Vq14v7e9z1_DUE_QPfor0O</recordid><startdate>20220125</startdate><enddate>20220125</enddate><creator>Almohaywi, Basmah</creator><creator>Yu, Tsz Tin</creator><creator>Iskander, George</creator><creator>Sabir, Shekh</creator><creator>Bhadbhade, Mohan</creator><creator>Black, David StC</creator><creator>Kumar, Naresh</creator><general>MDPI AG</general><general>MDPI</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7T7</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8484-7342</orcidid><orcidid>https://orcid.org/0000-0002-3962-3040</orcidid><orcidid>https://orcid.org/0000-0002-0951-9621</orcidid><orcidid>https://orcid.org/0000-0001-9300-4737</orcidid><orcidid>https://orcid.org/0000-0001-6389-3051</orcidid></search><sort><creationdate>20220125</creationdate><title>Synthesis of Alkyne-Substituted Dihydropyrrolones as Bacterial Quorum-Sensing Inhibitors of Pseudomonas aeruginosa</title><author>Almohaywi, Basmah ; Yu, Tsz Tin ; Iskander, George ; Sabir, Shekh ; Bhadbhade, Mohan ; Black, David StC ; Kumar, Naresh</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-6a568b47dde556bfb4a3e685bb8eb635a2c15cfdc633327b4c2281445a2494743</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Acetylene</topic><topic>alkyne synthesis</topic><topic>Alkynes</topic><topic>Amides</topic><topic>Antibiotics</topic><topic>Antimicrobial agents</topic><topic>Bacteria</topic><topic>Biofilms</topic><topic>Bromination</topic><topic>Carbon</topic><topic>Chemical reactions</topic><topic>dihydropyrrolones</topic><topic>Drug resistance</topic><topic>Inhibitors</topic><topic>Intermediates</topic><topic>Palladium</topic><topic>Pathogenicity</topic><topic>Pathogens</topic><topic>Pharmaceutical sciences</topic><topic>Phenotypes</topic><topic>Pseudomonas aeruginosa</topic><topic>quorum sensing</topic><topic>Solvents</topic><topic>Virulence</topic><topic>Virulence factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Almohaywi, Basmah</creatorcontrib><creatorcontrib>Yu, Tsz Tin</creatorcontrib><creatorcontrib>Iskander, George</creatorcontrib><creatorcontrib>Sabir, Shekh</creatorcontrib><creatorcontrib>Bhadbhade, Mohan</creatorcontrib><creatorcontrib>Black, David StC</creatorcontrib><creatorcontrib>Kumar, Naresh</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Databases</collection><collection>ProQuest Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Engineering Research Database</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>ProQuest Biological Science Journals</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>Antibiotics (Basel)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Almohaywi, Basmah</au><au>Yu, Tsz Tin</au><au>Iskander, George</au><au>Sabir, Shekh</au><au>Bhadbhade, Mohan</au><au>Black, David StC</au><au>Kumar, Naresh</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of Alkyne-Substituted Dihydropyrrolones as Bacterial Quorum-Sensing Inhibitors of Pseudomonas aeruginosa</atitle><jtitle>Antibiotics (Basel)</jtitle><addtitle>Antibiotics (Basel)</addtitle><date>2022-01-25</date><risdate>2022</risdate><volume>11</volume><issue>2</issue><spage>151</spage><pages>151-</pages><issn>2079-6382</issn><eissn>2079-6382</eissn><abstract>The Quorum-sensing system in
is responsible for the pathogenicity and the production of virulence factors and biofilm formation. Dihydropyrrolones were previously found to act as inhibitors of QS-dependent bacterial phenotypes. In this study, a range of dihydropyrrolone (DHP) analogues was synthesized via the lactone-lactam conversion of lactone intermediates followed by the formation of novel acetylene analogues of dihydropyrrolones from brominated dihydropyrrolones via Sonogashira coupling reactions in moderate to high yields. Upon biological testing, the most potent compounds,
-
and
showed higher bacterial quorum-sensing inhibitory (QSI) activity against
reporter strain at 62.5 µM. Structure-activity relationship studies revealed that di-alkynyl substituent at the exocyclic position of DHPs possessed higher QSI activities than those of mono-alkynyl DHPs. Moreover, a hexyl-substituent at C3 of DHPs was beneficial to QSI activity while a phenyl substituent at C4 of DHPs was detrimental to QSI activity of analogues.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>35203755</pmid><doi>10.3390/antibiotics11020151</doi><orcidid>https://orcid.org/0000-0002-8484-7342</orcidid><orcidid>https://orcid.org/0000-0002-3962-3040</orcidid><orcidid>https://orcid.org/0000-0002-0951-9621</orcidid><orcidid>https://orcid.org/0000-0001-9300-4737</orcidid><orcidid>https://orcid.org/0000-0001-6389-3051</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Antibiotics (Basel), 2022-01, Vol.11 (2), p.151 |
| issn | 2079-6382 2079-6382 |
| language | eng |
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| source | Publicly Available Content Database; PubMed Central |
| subjects | Acetylene alkyne synthesis Alkynes Amides Antibiotics Antimicrobial agents Bacteria Biofilms Bromination Carbon Chemical reactions dihydropyrrolones Drug resistance Inhibitors Intermediates Palladium Pathogenicity Pathogens Pharmaceutical sciences Phenotypes Pseudomonas aeruginosa quorum sensing Solvents Virulence Virulence factors |
| title | Synthesis of Alkyne-Substituted Dihydropyrrolones as Bacterial Quorum-Sensing Inhibitors of Pseudomonas aeruginosa |
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