Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria
Five novel N‐substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. The in vitro antibacterial activities against methicillin‐resistant Staphylococcus aureus (MRSA), gentamicin‐resistant Enterococcus faecalis (GRE), methicillin‐resist...
Gespeichert in:
| Veröffentlicht in: | ChemMedChem 2013-06, Vol.8 (6), p.976-984 |
|---|---|
| Hauptverfasser: | , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 984 |
|---|---|
| container_issue | 6 |
| container_start_page | 976 |
| container_title | ChemMedChem |
| container_volume | 8 |
| creator | Chang, Jun Zhang, Si-Ji Jiang, Yong-Wei Xu, Liang Yu, Jian-Ming Zhou, Wen-Jiang Sun, Xun |
| description | Five novel N‐substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. The in vitro antibacterial activities against methicillin‐resistant Staphylococcus aureus (MRSA), gentamicin‐resistant Enterococcus faecalis (GRE), methicillin‐resistant Streptococcus pneumoniae (MRS), and vancomycin‐resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N‐(6‐phenylheptyl)demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a was also found to be ∼18‐fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half‐life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.
The best of five: N‐Substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. One of the compounds was found to exhibit more potent antibacterial activity against drug‐resistant bacteria than vancomycin or demethylvancomycin, suggesting its promise as an antibacterial drug candidate. |
| doi_str_mv | 10.1002/cmdc.201300011 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1439235262</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1439235262</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4441-8c5c16d2f7c2f2c56a0cc020e87b15ff289a9430f857bfcbe5ed7821da5391f53</originalsourceid><addsrcrecordid>eNqFkc1v0zAYhyMEYh9w5YgiceGwFH_G9rG0rCAVmGBou1mOY3ceiTNsZ5D_HpeWCnHZye_h-T16_f6K4gUEMwgAeqP7Vs8QgBgAAOGj4hjyGlQMcvb4MDNxVJzEeAsAIRzyp8URwpTVmPHjol-a6Db-rPw6-XST53hWKt-Wc59co3QywamunOvk7l2aysGWS9ObdDN198rroZ-08xlW3bAZTSzVRjkfU7kM46b6stUl5VP5dm96Vjyxqovm-f49Lb6dv7tcvK_Wn1cfFvN1pQkhsOKaali3yDKNLNK0VkBrgIDhrIHUWsSFEgQDyylrrG4MNS3jCLaKYgEtxafF6533Lgw_8l5J9i5q03XKm2GMEhIs8g1QjR5GMa1xLTiBGX31H3o7jCH__Q9FYS2IYJma7SgdhhiDsfIuuF6FSUIgt53JbWfy0FkOvNxrx6Y37QH_W1IGxA746TozPaCTi4_Lxb_yapfNTZhfh6wK32XNMKPy6tNKXoP15cXV9Upe4N91mLJU</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1355169497</pqid></control><display><type>article</type><title>Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria</title><source>MEDLINE</source><source>Wiley Online Library All Journals</source><creator>Chang, Jun ; Zhang, Si-Ji ; Jiang, Yong-Wei ; Xu, Liang ; Yu, Jian-Ming ; Zhou, Wen-Jiang ; Sun, Xun</creator><creatorcontrib>Chang, Jun ; Zhang, Si-Ji ; Jiang, Yong-Wei ; Xu, Liang ; Yu, Jian-Ming ; Zhou, Wen-Jiang ; Sun, Xun</creatorcontrib><description>Five novel N‐substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. The in vitro antibacterial activities against methicillin‐resistant Staphylococcus aureus (MRSA), gentamicin‐resistant Enterococcus faecalis (GRE), methicillin‐resistant Streptococcus pneumoniae (MRS), and vancomycin‐resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N‐(6‐phenylheptyl)demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a was also found to be ∼18‐fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half‐life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.
The best of five: N‐Substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. One of the compounds was found to exhibit more potent antibacterial activity against drug‐resistant bacteria than vancomycin or demethylvancomycin, suggesting its promise as an antibacterial drug candidate.</description><identifier>ISSN: 1860-7179</identifier><identifier>EISSN: 1860-7187</identifier><identifier>DOI: 10.1002/cmdc.201300011</identifier><identifier>PMID: 23576378</identifier><language>eng</language><publisher>Weinheim: WILEY-VCH Verlag</publisher><subject>Anti-Bacterial Agents - chemical synthesis ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Antibacterial activity ; antibiotics ; demethylvancomycin ; Dose-Response Relationship, Drug ; Drug Design ; drug resistance ; Drug Resistance, Bacterial - drug effects ; Enterococcus faecalis ; Enterococcus faecalis - drug effects ; Methicillin-Resistant Staphylococcus aureus - drug effects ; Microbial Sensitivity Tests ; Models, Molecular ; Molecular Structure ; Streptococcus pneumoniae - drug effects ; Structure-Activity Relationship ; structure-activity relationships ; synthesis design ; Vancomycin - analogs & derivatives ; Vancomycin - chemical synthesis ; Vancomycin - pharmacology</subject><ispartof>ChemMedChem, 2013-06, Vol.8 (6), p.976-984</ispartof><rights>Copyright © 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim</rights><rights>Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.</rights><rights>Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4441-8c5c16d2f7c2f2c56a0cc020e87b15ff289a9430f857bfcbe5ed7821da5391f53</citedby><cites>FETCH-LOGICAL-c4441-8c5c16d2f7c2f2c56a0cc020e87b15ff289a9430f857bfcbe5ed7821da5391f53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcmdc.201300011$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcmdc.201300011$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23576378$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chang, Jun</creatorcontrib><creatorcontrib>Zhang, Si-Ji</creatorcontrib><creatorcontrib>Jiang, Yong-Wei</creatorcontrib><creatorcontrib>Xu, Liang</creatorcontrib><creatorcontrib>Yu, Jian-Ming</creatorcontrib><creatorcontrib>Zhou, Wen-Jiang</creatorcontrib><creatorcontrib>Sun, Xun</creatorcontrib><title>Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria</title><title>ChemMedChem</title><addtitle>ChemMedChem</addtitle><description>Five novel N‐substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. The in vitro antibacterial activities against methicillin‐resistant Staphylococcus aureus (MRSA), gentamicin‐resistant Enterococcus faecalis (GRE), methicillin‐resistant Streptococcus pneumoniae (MRS), and vancomycin‐resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N‐(6‐phenylheptyl)demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a was also found to be ∼18‐fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half‐life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.
The best of five: N‐Substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. One of the compounds was found to exhibit more potent antibacterial activity against drug‐resistant bacteria than vancomycin or demethylvancomycin, suggesting its promise as an antibacterial drug candidate.</description><subject>Anti-Bacterial Agents - chemical synthesis</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibacterial activity</subject><subject>antibiotics</subject><subject>demethylvancomycin</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>drug resistance</subject><subject>Drug Resistance, Bacterial - drug effects</subject><subject>Enterococcus faecalis</subject><subject>Enterococcus faecalis - drug effects</subject><subject>Methicillin-Resistant Staphylococcus aureus - drug effects</subject><subject>Microbial Sensitivity Tests</subject><subject>Models, Molecular</subject><subject>Molecular Structure</subject><subject>Streptococcus pneumoniae - drug effects</subject><subject>Structure-Activity Relationship</subject><subject>structure-activity relationships</subject><subject>synthesis design</subject><subject>Vancomycin - analogs & derivatives</subject><subject>Vancomycin - chemical synthesis</subject><subject>Vancomycin - pharmacology</subject><issn>1860-7179</issn><issn>1860-7187</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v0zAYhyMEYh9w5YgiceGwFH_G9rG0rCAVmGBou1mOY3ceiTNsZ5D_HpeWCnHZye_h-T16_f6K4gUEMwgAeqP7Vs8QgBgAAOGj4hjyGlQMcvb4MDNxVJzEeAsAIRzyp8URwpTVmPHjol-a6Db-rPw6-XST53hWKt-Wc59co3QywamunOvk7l2aysGWS9ObdDN198rroZ-08xlW3bAZTSzVRjkfU7kM46b6stUl5VP5dm96Vjyxqovm-f49Lb6dv7tcvK_Wn1cfFvN1pQkhsOKaali3yDKNLNK0VkBrgIDhrIHUWsSFEgQDyylrrG4MNS3jCLaKYgEtxafF6533Lgw_8l5J9i5q03XKm2GMEhIs8g1QjR5GMa1xLTiBGX31H3o7jCH__Q9FYS2IYJma7SgdhhiDsfIuuF6FSUIgt53JbWfy0FkOvNxrx6Y37QH_W1IGxA746TozPaCTi4_Lxb_yapfNTZhfh6wK32XNMKPy6tNKXoP15cXV9Upe4N91mLJU</recordid><startdate>201306</startdate><enddate>201306</enddate><creator>Chang, Jun</creator><creator>Zhang, Si-Ji</creator><creator>Jiang, Yong-Wei</creator><creator>Xu, Liang</creator><creator>Yu, Jian-Ming</creator><creator>Zhou, Wen-Jiang</creator><creator>Sun, Xun</creator><general>WILEY-VCH Verlag</general><general>WILEY‐VCH Verlag</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7TK</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>K9.</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>7QL</scope><scope>7T7</scope></search><sort><creationdate>201306</creationdate><title>Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria</title><author>Chang, Jun ; Zhang, Si-Ji ; Jiang, Yong-Wei ; Xu, Liang ; Yu, Jian-Ming ; Zhou, Wen-Jiang ; Sun, Xun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4441-8c5c16d2f7c2f2c56a0cc020e87b15ff289a9430f857bfcbe5ed7821da5391f53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Anti-Bacterial Agents - chemical synthesis</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibacterial activity</topic><topic>antibiotics</topic><topic>demethylvancomycin</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Design</topic><topic>drug resistance</topic><topic>Drug Resistance, Bacterial - drug effects</topic><topic>Enterococcus faecalis</topic><topic>Enterococcus faecalis - drug effects</topic><topic>Methicillin-Resistant Staphylococcus aureus - drug effects</topic><topic>Microbial Sensitivity Tests</topic><topic>Models, Molecular</topic><topic>Molecular Structure</topic><topic>Streptococcus pneumoniae - drug effects</topic><topic>Structure-Activity Relationship</topic><topic>structure-activity relationships</topic><topic>synthesis design</topic><topic>Vancomycin - analogs & derivatives</topic><topic>Vancomycin - chemical synthesis</topic><topic>Vancomycin - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chang, Jun</creatorcontrib><creatorcontrib>Zhang, Si-Ji</creatorcontrib><creatorcontrib>Jiang, Yong-Wei</creatorcontrib><creatorcontrib>Xu, Liang</creatorcontrib><creatorcontrib>Yu, Jian-Ming</creatorcontrib><creatorcontrib>Zhou, Wen-Jiang</creatorcontrib><creatorcontrib>Sun, Xun</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><jtitle>ChemMedChem</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chang, Jun</au><au>Zhang, Si-Ji</au><au>Jiang, Yong-Wei</au><au>Xu, Liang</au><au>Yu, Jian-Ming</au><au>Zhou, Wen-Jiang</au><au>Sun, Xun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria</atitle><jtitle>ChemMedChem</jtitle><addtitle>ChemMedChem</addtitle><date>2013-06</date><risdate>2013</risdate><volume>8</volume><issue>6</issue><spage>976</spage><epage>984</epage><pages>976-984</pages><issn>1860-7179</issn><eissn>1860-7187</eissn><abstract>Five novel N‐substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. The in vitro antibacterial activities against methicillin‐resistant Staphylococcus aureus (MRSA), gentamicin‐resistant Enterococcus faecalis (GRE), methicillin‐resistant Streptococcus pneumoniae (MRS), and vancomycin‐resistant Enterococcus faecalis (VRE) were evaluated. One of the compounds, N‐(6‐phenylheptyl)demethylvancomycin (12 a), was found to exhibit more potent antibacterial activity than vancomycin and demethylvancomycin. Compound 12 a was also found to be ∼18‐fold more efficacious than vancomycin against MRSA; however, the two compounds were found to have similar efficacy against MRS. Furthermore, compound 12 a exhibited a favorable pharmacokinetic profile with a half‐life of 5.11±0.52 h, which is longer than that of vancomycin (4.3±1.9 h). These results suggest that 12 a is a promising antibacterial drug candidate for further preclinical evaluation.
The best of five: N‐Substituted demethylvancomycin derivatives were rationally designed and synthesized by using a structure‐based approach. One of the compounds was found to exhibit more potent antibacterial activity against drug‐resistant bacteria than vancomycin or demethylvancomycin, suggesting its promise as an antibacterial drug candidate.</abstract><cop>Weinheim</cop><pub>WILEY-VCH Verlag</pub><pmid>23576378</pmid><doi>10.1002/cmdc.201300011</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1860-7179 |
| ispartof | ChemMedChem, 2013-06, Vol.8 (6), p.976-984 |
| issn | 1860-7179 1860-7187 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_1439235262 |
| source | MEDLINE; Wiley Online Library All Journals |
| subjects | Anti-Bacterial Agents - chemical synthesis Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Antibacterial activity antibiotics demethylvancomycin Dose-Response Relationship, Drug Drug Design drug resistance Drug Resistance, Bacterial - drug effects Enterococcus faecalis Enterococcus faecalis - drug effects Methicillin-Resistant Staphylococcus aureus - drug effects Microbial Sensitivity Tests Models, Molecular Molecular Structure Streptococcus pneumoniae - drug effects Structure-Activity Relationship structure-activity relationships synthesis design Vancomycin - analogs & derivatives Vancomycin - chemical synthesis Vancomycin - pharmacology |
| title | Design, Synthesis, and Antibacterial Activity of Demethylvancomycin Analogues against Drug-Resistant Bacteria |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-06T17%3A25%3A50IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Design,%20Synthesis,%20and%20Antibacterial%20Activity%20of%20Demethylvancomycin%20Analogues%20against%20Drug-Resistant%20Bacteria&rft.jtitle=ChemMedChem&rft.au=Chang,%20Jun&rft.date=2013-06&rft.volume=8&rft.issue=6&rft.spage=976&rft.epage=984&rft.pages=976-984&rft.issn=1860-7179&rft.eissn=1860-7187&rft_id=info:doi/10.1002/cmdc.201300011&rft_dat=%3Cproquest_cross%3E1439235262%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1355169497&rft_id=info:pmid/23576378&rfr_iscdi=true |