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Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space
[Display omitted] We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular targ...
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| Published in: | Bioorganic & medicinal chemistry letters 2015-09, Vol.25 (17), p.3468-3475 |
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| Main Authors: | , , , , , , , , , |
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| Language: | English |
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| cited_by | cdi_FETCH-LOGICAL-c356t-8f63124fca909131d2e2d3e8ead939b546377bec97d6d18839735f8bee3b91fb3 |
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| cites | cdi_FETCH-LOGICAL-c356t-8f63124fca909131d2e2d3e8ead939b546377bec97d6d18839735f8bee3b91fb3 |
| container_end_page | 3475 |
| container_issue | 17 |
| container_start_page | 3468 |
| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 25 |
| creator | Ross, Audrey G. Benton, Bret M. Chin, Donovan De Pascale, Gianfranco Fuller, John Leeds, Jennifer A. Reck, Folkert Richie, Daryl L. Vo, Jason LaMarche, Matthew J. |
| description | [Display omitted]
We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular target (DNA gyrase), and translation to antibacterial activity in whole cells was demonstrated. Overall, cell permeation was governed by physicochemical properties and bacterial type. A principal component analysis demonstrated that the dimers occupy a unique and privileged region of chemical space most similar to the macrolide class of antibiotics. |
| doi_str_mv | 10.1016/j.bmcl.2015.07.010 |
| format | article |
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We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular target (DNA gyrase), and translation to antibacterial activity in whole cells was demonstrated. Overall, cell permeation was governed by physicochemical properties and bacterial type. A principal component analysis demonstrated that the dimers occupy a unique and privileged region of chemical space most similar to the macrolide class of antibiotics.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2015.07.010</identifier><identifier>PMID: 26189081</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Anti-Bacterial Agents - chemical synthesis ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Anti-Infective Agents - chemical synthesis ; Anti-Infective Agents - chemistry ; Anti-Infective Agents - pharmacology ; Antibacterial ; Antibiotic ; Bacterial permeability ; Chemical space ; Ciprofloxacin - chemical synthesis ; Ciprofloxacin - chemistry ; Ciprofloxacin - pharmacology ; Dimer ; DNA gyrase ; DNA, Bacterial - metabolism ; Fluoroquinolone ; Middle space ; Permeability</subject><ispartof>Bioorganic & medicinal chemistry letters, 2015-09, Vol.25 (17), p.3468-3475</ispartof><rights>2015 Elsevier Ltd</rights><rights>Copyright © 2015 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c356t-8f63124fca909131d2e2d3e8ead939b546377bec97d6d18839735f8bee3b91fb3</citedby><cites>FETCH-LOGICAL-c356t-8f63124fca909131d2e2d3e8ead939b546377bec97d6d18839735f8bee3b91fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26189081$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ross, Audrey G.</creatorcontrib><creatorcontrib>Benton, Bret M.</creatorcontrib><creatorcontrib>Chin, Donovan</creatorcontrib><creatorcontrib>De Pascale, Gianfranco</creatorcontrib><creatorcontrib>Fuller, John</creatorcontrib><creatorcontrib>Leeds, Jennifer A.</creatorcontrib><creatorcontrib>Reck, Folkert</creatorcontrib><creatorcontrib>Richie, Daryl L.</creatorcontrib><creatorcontrib>Vo, Jason</creatorcontrib><creatorcontrib>LaMarche, Matthew J.</creatorcontrib><title>Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular target (DNA gyrase), and translation to antibacterial activity in whole cells was demonstrated. Overall, cell permeation was governed by physicochemical properties and bacterial type. A principal component analysis demonstrated that the dimers occupy a unique and privileged region of chemical space most similar to the macrolide class of antibiotics.</description><subject>Anti-Bacterial Agents - chemical synthesis</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Anti-Infective Agents - chemical synthesis</subject><subject>Anti-Infective Agents - chemistry</subject><subject>Anti-Infective Agents - pharmacology</subject><subject>Antibacterial</subject><subject>Antibiotic</subject><subject>Bacterial permeability</subject><subject>Chemical space</subject><subject>Ciprofloxacin - chemical synthesis</subject><subject>Ciprofloxacin - chemistry</subject><subject>Ciprofloxacin - pharmacology</subject><subject>Dimer</subject><subject>DNA gyrase</subject><subject>DNA, Bacterial - metabolism</subject><subject>Fluoroquinolone</subject><subject>Middle space</subject><subject>Permeability</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><recordid>eNp9kE1r3DAQhkVJaLZp_0APxcdc7MxYsmxBLiX0CwI5JIHchD5GRIu_KnlD9t_X20167GkG5nlfmIexzwgVAsrLbWUH11c1YFNBWwHCO7ZBIUXJBTQnbANKQtkp8XjGPuS8BUABQrxnZ7XETkGHG0Z3-3F5ohxzMYXCxTlNoZ9ejItj4eNAKRdhSgU9m35nljiNB8wat1CKpi9mSgMZG_u47Is1Ypb9HN16cE80_F3ybBx9ZKfB9Jk-vc5z9vD92_31z_Lm9sev6683peONXMouSI61CM4oUMjR11R7Th0Zr7iyjZC8bS051Xrpseu4ankTOkvErcJg-Tm7OPaub_zeUV70ELOjvjcjTbussQXkteBSrWh9RF2ack4U9JziYNJeI-iDXr3VB736oFdDq1e9a-jLa__ODuT_Rd58rsDVEaD1y-dISWcXaXTkYyK3aD_F__X_AeF-jWE</recordid><startdate>20150901</startdate><enddate>20150901</enddate><creator>Ross, Audrey G.</creator><creator>Benton, Bret M.</creator><creator>Chin, Donovan</creator><creator>De Pascale, Gianfranco</creator><creator>Fuller, John</creator><creator>Leeds, Jennifer A.</creator><creator>Reck, Folkert</creator><creator>Richie, Daryl L.</creator><creator>Vo, Jason</creator><creator>LaMarche, Matthew J.</creator><general>Elsevier Ltd</general><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>7X8</scope></search><sort><creationdate>20150901</creationdate><title>Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space</title><author>Ross, Audrey G. ; Benton, Bret M. ; Chin, Donovan ; De Pascale, Gianfranco ; Fuller, John ; Leeds, Jennifer A. ; Reck, Folkert ; Richie, Daryl L. ; Vo, Jason ; LaMarche, Matthew J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c356t-8f63124fca909131d2e2d3e8ead939b546377bec97d6d18839735f8bee3b91fb3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Anti-Bacterial Agents - chemical synthesis</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Anti-Infective Agents - chemical synthesis</topic><topic>Anti-Infective Agents - chemistry</topic><topic>Anti-Infective Agents - pharmacology</topic><topic>Antibacterial</topic><topic>Antibiotic</topic><topic>Bacterial permeability</topic><topic>Chemical space</topic><topic>Ciprofloxacin - chemical synthesis</topic><topic>Ciprofloxacin - chemistry</topic><topic>Ciprofloxacin - pharmacology</topic><topic>Dimer</topic><topic>DNA gyrase</topic><topic>DNA, Bacterial - metabolism</topic><topic>Fluoroquinolone</topic><topic>Middle space</topic><topic>Permeability</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ross, Audrey G.</creatorcontrib><creatorcontrib>Benton, Bret M.</creatorcontrib><creatorcontrib>Chin, Donovan</creatorcontrib><creatorcontrib>De Pascale, Gianfranco</creatorcontrib><creatorcontrib>Fuller, John</creatorcontrib><creatorcontrib>Leeds, Jennifer A.</creatorcontrib><creatorcontrib>Reck, Folkert</creatorcontrib><creatorcontrib>Richie, Daryl L.</creatorcontrib><creatorcontrib>Vo, Jason</creatorcontrib><creatorcontrib>LaMarche, Matthew J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ross, Audrey G.</au><au>Benton, Bret M.</au><au>Chin, Donovan</au><au>De Pascale, Gianfranco</au><au>Fuller, John</au><au>Leeds, Jennifer A.</au><au>Reck, Folkert</au><au>Richie, Daryl L.</au><au>Vo, Jason</au><au>LaMarche, Matthew J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2015-09-01</date><risdate>2015</risdate><volume>25</volume><issue>17</issue><spage>3468</spage><epage>3475</epage><pages>3468-3475</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular target (DNA gyrase), and translation to antibacterial activity in whole cells was demonstrated. Overall, cell permeation was governed by physicochemical properties and bacterial type. A principal component analysis demonstrated that the dimers occupy a unique and privileged region of chemical space most similar to the macrolide class of antibiotics.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>26189081</pmid><doi>10.1016/j.bmcl.2015.07.010</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2015-09, Vol.25 (17), p.3468-3475 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | ScienceDirect Freedom Collection |
| subjects | Anti-Bacterial Agents - chemical synthesis Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Anti-Infective Agents - chemical synthesis Anti-Infective Agents - chemistry Anti-Infective Agents - pharmacology Antibacterial Antibiotic Bacterial permeability Chemical space Ciprofloxacin - chemical synthesis Ciprofloxacin - chemistry Ciprofloxacin - pharmacology Dimer DNA gyrase DNA, Bacterial - metabolism Fluoroquinolone Middle space Permeability |
| title | Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space |
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