Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs
Our aim was to identify new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant . E...
Gespeichert in:
| Veröffentlicht in: | MedChemComm 2018-06, Vol.9 (6), p.1017-1032 |
|---|---|
| Hauptverfasser: | , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1032 |
|---|---|
| container_issue | 6 |
| container_start_page | 1017 |
| container_title | MedChemComm |
| container_volume | 9 |
| creator | Carta, Davide Brun, Paola Dal Pra, Matteo Bernabè, Giulia Castagliuolo, Ignazio Ferlin, Maria Grazia |
| description | Our aim was to identify new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant
. Effective synthesis of some aza-analogs of the anti-inflammatory drug diflunisal was carried out following the route involving key oxazole intermediates to obtain
- and
-hydroxypyridinecarboxylic acid derivatives. The newly synthesized diflunisal aza-analogs did not exhibit cytotoxic activity up to 80 μM and some of them exhibited anti-inflammatory activities, decreasing the levels of pro-inflammatory cytokines and prostaglandins induced by bacterial lipopolysaccharide in human primary macrophages. Ten of the diflunisal aza-analogs were found to have interesting antibacterial activity, sensitizing
,
,
, and
to the antibacterial effects of beta-lactam antibiotics and protein synthesis inhibitors. |
| doi_str_mv | 10.1039/c8md00139a |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6071938</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2088756846</sourcerecordid><originalsourceid>FETCH-LOGICAL-c447t-f38b30a2f47feefb88f6c03de04c214ce67df7d42eb448b12004baf7e0c738a23</originalsourceid><addsrcrecordid>eNpdkV1rFDEUhoMottTe-ANkwBsRRk8-dpK5EcrWj0KlF9XrcCaTdFMyyZrMFOqvN9utizY3yTnn4eU9eQl5TeEDBd5_NGoaASjv8Rk5ZiCgZStKnx_ewI_IaSm3UA9nSvXiJTniQEH1PT0mm-v7OG9s8aXBODbbbIOffMR8X-vZtz66gNOEc3rojPvugGa22WNo7B2GBWefYpNcU9Jkm9G7sERf6hR_Y4sRQ7opr8gLh6HY08f7hPz88vnH-lt7efX1Yn122Roh5Nw6rgYOyJyQzlo3KOU6A3y0IAyjwthOjk6OgtlBCDVQBiAGdNKCkVwh4yfk0153uwyTHY2Nc8agt9lPdSmd0Ov_J9Fv9E260x1I2nNVBd49CuT0a7Fl1pMvxoaA0aalaAZKyVWnRFfRt0_Q27Tkuu-OWsn6-Qx2jt7vKZNTKdm6gxkKepehXqvv5w8ZnlX4zb_2D-jfxPgfeD6ZkQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2057250202</pqid></control><display><type>article</type><title>Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs</title><source>Royal Society Of Chemistry Journals 2008-</source><source>PubMed Central</source><creator>Carta, Davide ; Brun, Paola ; Dal Pra, Matteo ; Bernabè, Giulia ; Castagliuolo, Ignazio ; Ferlin, Maria Grazia</creator><creatorcontrib>Carta, Davide ; Brun, Paola ; Dal Pra, Matteo ; Bernabè, Giulia ; Castagliuolo, Ignazio ; Ferlin, Maria Grazia</creatorcontrib><description>Our aim was to identify new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant
. Effective synthesis of some aza-analogs of the anti-inflammatory drug diflunisal was carried out following the route involving key oxazole intermediates to obtain
- and
-hydroxypyridinecarboxylic acid derivatives. The newly synthesized diflunisal aza-analogs did not exhibit cytotoxic activity up to 80 μM and some of them exhibited anti-inflammatory activities, decreasing the levels of pro-inflammatory cytokines and prostaglandins induced by bacterial lipopolysaccharide in human primary macrophages. Ten of the diflunisal aza-analogs were found to have interesting antibacterial activity, sensitizing
,
,
, and
to the antibacterial effects of beta-lactam antibiotics and protein synthesis inhibitors.</description><identifier>ISSN: 2040-2503</identifier><identifier>EISSN: 2040-2511</identifier><identifier>DOI: 10.1039/c8md00139a</identifier><identifier>PMID: 30108991</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Amides ; Analogs ; Antibacterial activity ; Antibiotics ; Bacteria ; Chemistry ; Cytokines ; Cytotoxicity ; Drug resistance ; Inflammation ; Intermediates ; Lipopolysaccharides ; Macrophages ; Methicillin ; Oxazole ; Penicillin ; Prostaglandins ; Protein biosynthesis ; Protein synthesis ; Proteins ; Pseudomonas aeruginosa ; Sensitizing ; Staphylococcus infections ; Streptococcus infections ; Target recognition ; Virulence ; β-Lactam antibiotics</subject><ispartof>MedChemComm, 2018-06, Vol.9 (6), p.1017-1032</ispartof><rights>Copyright Royal Society of Chemistry 2018</rights><rights>This journal is © The Royal Society of Chemistry 2018 2018</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c447t-f38b30a2f47feefb88f6c03de04c214ce67df7d42eb448b12004baf7e0c738a23</citedby><cites>FETCH-LOGICAL-c447t-f38b30a2f47feefb88f6c03de04c214ce67df7d42eb448b12004baf7e0c738a23</cites><orcidid>0000-0003-0762-7933 ; 0000-0002-3279-9000</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071938/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6071938/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30108991$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Carta, Davide</creatorcontrib><creatorcontrib>Brun, Paola</creatorcontrib><creatorcontrib>Dal Pra, Matteo</creatorcontrib><creatorcontrib>Bernabè, Giulia</creatorcontrib><creatorcontrib>Castagliuolo, Ignazio</creatorcontrib><creatorcontrib>Ferlin, Maria Grazia</creatorcontrib><title>Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs</title><title>MedChemComm</title><addtitle>Medchemcomm</addtitle><description>Our aim was to identify new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant
. Effective synthesis of some aza-analogs of the anti-inflammatory drug diflunisal was carried out following the route involving key oxazole intermediates to obtain
- and
-hydroxypyridinecarboxylic acid derivatives. The newly synthesized diflunisal aza-analogs did not exhibit cytotoxic activity up to 80 μM and some of them exhibited anti-inflammatory activities, decreasing the levels of pro-inflammatory cytokines and prostaglandins induced by bacterial lipopolysaccharide in human primary macrophages. Ten of the diflunisal aza-analogs were found to have interesting antibacterial activity, sensitizing
,
,
, and
to the antibacterial effects of beta-lactam antibiotics and protein synthesis inhibitors.</description><subject>Amides</subject><subject>Analogs</subject><subject>Antibacterial activity</subject><subject>Antibiotics</subject><subject>Bacteria</subject><subject>Chemistry</subject><subject>Cytokines</subject><subject>Cytotoxicity</subject><subject>Drug resistance</subject><subject>Inflammation</subject><subject>Intermediates</subject><subject>Lipopolysaccharides</subject><subject>Macrophages</subject><subject>Methicillin</subject><subject>Oxazole</subject><subject>Penicillin</subject><subject>Prostaglandins</subject><subject>Protein biosynthesis</subject><subject>Protein synthesis</subject><subject>Proteins</subject><subject>Pseudomonas aeruginosa</subject><subject>Sensitizing</subject><subject>Staphylococcus infections</subject><subject>Streptococcus infections</subject><subject>Target recognition</subject><subject>Virulence</subject><subject>β-Lactam antibiotics</subject><issn>2040-2503</issn><issn>2040-2511</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNpdkV1rFDEUhoMottTe-ANkwBsRRk8-dpK5EcrWj0KlF9XrcCaTdFMyyZrMFOqvN9utizY3yTnn4eU9eQl5TeEDBd5_NGoaASjv8Rk5ZiCgZStKnx_ewI_IaSm3UA9nSvXiJTniQEH1PT0mm-v7OG9s8aXBODbbbIOffMR8X-vZtz66gNOEc3rojPvugGa22WNo7B2GBWefYpNcU9Jkm9G7sERf6hR_Y4sRQ7opr8gLh6HY08f7hPz88vnH-lt7efX1Yn122Roh5Nw6rgYOyJyQzlo3KOU6A3y0IAyjwthOjk6OgtlBCDVQBiAGdNKCkVwh4yfk0153uwyTHY2Nc8agt9lPdSmd0Ov_J9Fv9E260x1I2nNVBd49CuT0a7Fl1pMvxoaA0aalaAZKyVWnRFfRt0_Q27Tkuu-OWsn6-Qx2jt7vKZNTKdm6gxkKepehXqvv5w8ZnlX4zb_2D-jfxPgfeD6ZkQ</recordid><startdate>20180601</startdate><enddate>20180601</enddate><creator>Carta, Davide</creator><creator>Brun, Paola</creator><creator>Dal Pra, Matteo</creator><creator>Bernabè, Giulia</creator><creator>Castagliuolo, Ignazio</creator><creator>Ferlin, Maria Grazia</creator><general>Royal Society of Chemistry</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QL</scope><scope>7QO</scope><scope>7T5</scope><scope>7T7</scope><scope>7TO</scope><scope>7U7</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-0762-7933</orcidid><orcidid>https://orcid.org/0000-0002-3279-9000</orcidid></search><sort><creationdate>20180601</creationdate><title>Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs</title><author>Carta, Davide ; Brun, Paola ; Dal Pra, Matteo ; Bernabè, Giulia ; Castagliuolo, Ignazio ; Ferlin, Maria Grazia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-f38b30a2f47feefb88f6c03de04c214ce67df7d42eb448b12004baf7e0c738a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Amides</topic><topic>Analogs</topic><topic>Antibacterial activity</topic><topic>Antibiotics</topic><topic>Bacteria</topic><topic>Chemistry</topic><topic>Cytokines</topic><topic>Cytotoxicity</topic><topic>Drug resistance</topic><topic>Inflammation</topic><topic>Intermediates</topic><topic>Lipopolysaccharides</topic><topic>Macrophages</topic><topic>Methicillin</topic><topic>Oxazole</topic><topic>Penicillin</topic><topic>Prostaglandins</topic><topic>Protein biosynthesis</topic><topic>Protein synthesis</topic><topic>Proteins</topic><topic>Pseudomonas aeruginosa</topic><topic>Sensitizing</topic><topic>Staphylococcus infections</topic><topic>Streptococcus infections</topic><topic>Target recognition</topic><topic>Virulence</topic><topic>β-Lactam antibiotics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carta, Davide</creatorcontrib><creatorcontrib>Brun, Paola</creatorcontrib><creatorcontrib>Dal Pra, Matteo</creatorcontrib><creatorcontrib>Bernabè, Giulia</creatorcontrib><creatorcontrib>Castagliuolo, Ignazio</creatorcontrib><creatorcontrib>Ferlin, Maria Grazia</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>MedChemComm</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carta, Davide</au><au>Brun, Paola</au><au>Dal Pra, Matteo</au><au>Bernabè, Giulia</au><au>Castagliuolo, Ignazio</au><au>Ferlin, Maria Grazia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs</atitle><jtitle>MedChemComm</jtitle><addtitle>Medchemcomm</addtitle><date>2018-06-01</date><risdate>2018</risdate><volume>9</volume><issue>6</issue><spage>1017</spage><epage>1032</epage><pages>1017-1032</pages><issn>2040-2503</issn><eissn>2040-2511</eissn><abstract>Our aim was to identify new multi-target compounds endowed with both anti-inflammatory and anti-bacterial activities for treatment of human infections. Diflunisal, a nonsteroidal anti-inflammatory agent, has recently been repurposed for its anti-virulence properties against methicillin-resistant
. Effective synthesis of some aza-analogs of the anti-inflammatory drug diflunisal was carried out following the route involving key oxazole intermediates to obtain
- and
-hydroxypyridinecarboxylic acid derivatives. The newly synthesized diflunisal aza-analogs did not exhibit cytotoxic activity up to 80 μM and some of them exhibited anti-inflammatory activities, decreasing the levels of pro-inflammatory cytokines and prostaglandins induced by bacterial lipopolysaccharide in human primary macrophages. Ten of the diflunisal aza-analogs were found to have interesting antibacterial activity, sensitizing
,
,
, and
to the antibacterial effects of beta-lactam antibiotics and protein synthesis inhibitors.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>30108991</pmid><doi>10.1039/c8md00139a</doi><tpages>16</tpages><orcidid>https://orcid.org/0000-0003-0762-7933</orcidid><orcidid>https://orcid.org/0000-0002-3279-9000</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2040-2503 |
| ispartof | MedChemComm, 2018-06, Vol.9 (6), p.1017-1032 |
| issn | 2040-2503 2040-2511 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6071938 |
| source | Royal Society Of Chemistry Journals 2008-; PubMed Central |
| subjects | Amides Analogs Antibacterial activity Antibiotics Bacteria Chemistry Cytokines Cytotoxicity Drug resistance Inflammation Intermediates Lipopolysaccharides Macrophages Methicillin Oxazole Penicillin Prostaglandins Protein biosynthesis Protein synthesis Proteins Pseudomonas aeruginosa Sensitizing Staphylococcus infections Streptococcus infections Target recognition Virulence β-Lactam antibiotics |
| title | Synthesis and preliminary anti-inflammatory and anti-bacterial evaluation of some diflunisal aza-analogs |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-23T17%3A56%3A32IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Synthesis%20and%20preliminary%20anti-inflammatory%20and%20anti-bacterial%20evaluation%20of%20some%20diflunisal%20aza-analogs&rft.jtitle=MedChemComm&rft.au=Carta,%20Davide&rft.date=2018-06-01&rft.volume=9&rft.issue=6&rft.spage=1017&rft.epage=1032&rft.pages=1017-1032&rft.issn=2040-2503&rft.eissn=2040-2511&rft_id=info:doi/10.1039/c8md00139a&rft_dat=%3Cproquest_pubme%3E2088756846%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2057250202&rft_id=info:pmid/30108991&rfr_iscdi=true |