Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII
A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA) inhibitors and synthesized. Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA) and isothermal titration calorimetry (ITC). Saccharin bound the CAs...
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| Veröffentlicht in: | BioMed research international 2014-01, Vol.2014 (2014), p.1-9 |
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| creator | Matulis, Daumantas Ivanova, Jekaterina Kairys, Visvaldas Zubrienė, Asta Baranauskienė, Lina Morkūnaitė, Vaida Trapencieris, Pēteris |
| description | A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA) inhibitors and synthesized. Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA) and isothermal titration calorimetry (ITC). Saccharin bound the CAs weakly, exhibiting the affinities of 1–10 mM for four CAs except CA I where binding could not be detected. Several sulfonamide-bearing saccharines exhibited strong affinities of 1–10 nM towards particular CA isoforms. The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs. |
| doi_str_mv | 10.1155/2014/638902 |
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Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA) and isothermal titration calorimetry (ITC). Saccharin bound the CAs weakly, exhibiting the affinities of 1–10 mM for four CAs except CA I where binding could not be detected. Several sulfonamide-bearing saccharines exhibited strong affinities of 1–10 nM towards particular CA isoforms. The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2014/638902</identifier><identifier>PMID: 25276805</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Calorimetry ; Carbonic Anhydrase Inhibitors - chemistry ; Carbonic Anhydrase Inhibitors - pharmacology ; Carbonic Anhydrases - metabolism ; Control ; Enzymes ; Experiments ; Fluorescence ; Health aspects ; Humans ; Isoenzymes - antagonists & inhibitors ; Isoenzymes - metabolism ; Ligands ; Methods ; Molecular Docking Simulation ; Physiological aspects ; Proteins ; Recombinant Proteins - metabolism ; Saccharin - chemistry ; Saccharin - pharmacology ; Studies ; Sulfonamides ; Sulfonamides - chemistry ; Sulfonamides - pharmacology ; Temperature ; Thermodynamics</subject><ispartof>BioMed research international, 2014-01, Vol.2014 (2014), p.1-9</ispartof><rights>Copyright © 2014 Vaida Morkūnaitė et al.</rights><rights>COPYRIGHT 2014 John Wiley & Sons, Inc.</rights><rights>Copyright © 2014 Vaida Morkunaite et al. Vaida Morkunaite et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</rights><rights>Copyright © 2014 Vaida Morkūnaitė et al. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c528t-e216463e2c8c02a212720148547b2a7c1bff85064251898f3958a1393bfef0c23</citedby><cites>FETCH-LOGICAL-c528t-e216463e2c8c02a212720148547b2a7c1bff85064251898f3958a1393bfef0c23</cites><orcidid>0000-0001-8845-0193 ; 0000-0002-5427-0175 ; 0000-0002-6178-6276</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/PMC4168026/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4168026/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25276805$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Alterio, Vincenzo</contributor><creatorcontrib>Matulis, Daumantas</creatorcontrib><creatorcontrib>Ivanova, Jekaterina</creatorcontrib><creatorcontrib>Kairys, Visvaldas</creatorcontrib><creatorcontrib>Zubrienė, Asta</creatorcontrib><creatorcontrib>Baranauskienė, Lina</creatorcontrib><creatorcontrib>Morkūnaitė, Vaida</creatorcontrib><creatorcontrib>Trapencieris, Pēteris</creatorcontrib><title>Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA) inhibitors and synthesized. 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The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs.</description><subject>Calorimetry</subject><subject>Carbonic Anhydrase Inhibitors - chemistry</subject><subject>Carbonic Anhydrase Inhibitors - pharmacology</subject><subject>Carbonic Anhydrases - metabolism</subject><subject>Control</subject><subject>Enzymes</subject><subject>Experiments</subject><subject>Fluorescence</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Isoenzymes - antagonists & inhibitors</subject><subject>Isoenzymes - metabolism</subject><subject>Ligands</subject><subject>Methods</subject><subject>Molecular Docking Simulation</subject><subject>Physiological aspects</subject><subject>Proteins</subject><subject>Recombinant Proteins - metabolism</subject><subject>Saccharin - chemistry</subject><subject>Saccharin - pharmacology</subject><subject>Studies</subject><subject>Sulfonamides</subject><subject>Sulfonamides - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Matulis, Daumantas</au><au>Ivanova, Jekaterina</au><au>Kairys, Visvaldas</au><au>Zubrienė, Asta</au><au>Baranauskienė, Lina</au><au>Morkūnaitė, Vaida</au><au>Trapencieris, Pēteris</au><au>Alterio, Vincenzo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>2014</volume><issue>2014</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>A series of modified saccharin sulfonamides have been designed as carbonic anhydrase (CA) inhibitors and synthesized. Their binding to CA isoforms I, II, VII, XII, and XIII was measured by the fluorescent thermal shift assay (FTSA) and isothermal titration calorimetry (ITC). Saccharin bound the CAs weakly, exhibiting the affinities of 1–10 mM for four CAs except CA I where binding could not be detected. Several sulfonamide-bearing saccharines exhibited strong affinities of 1–10 nM towards particular CA isoforms. The functional group binding Gibbs free energy additivity maps are presented which may provide insights into the design of compounds with increased affinity towards selected CAs.</abstract><cop>Cairo, Egypt</cop><pub>Hindawi Publishing Corporation</pub><pmid>25276805</pmid><doi>10.1155/2014/638902</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-8845-0193</orcidid><orcidid>https://orcid.org/0000-0002-5427-0175</orcidid><orcidid>https://orcid.org/0000-0002-6178-6276</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Calorimetry Carbonic Anhydrase Inhibitors - chemistry Carbonic Anhydrase Inhibitors - pharmacology Carbonic Anhydrases - metabolism Control Enzymes Experiments Fluorescence Health aspects Humans Isoenzymes - antagonists & inhibitors Isoenzymes - metabolism Ligands Methods Molecular Docking Simulation Physiological aspects Proteins Recombinant Proteins - metabolism Saccharin - chemistry Saccharin - pharmacology Studies Sulfonamides Sulfonamides - chemistry Sulfonamides - pharmacology Temperature Thermodynamics |
| title | Saccharin Sulfonamides as Inhibitors of Carbonic Anhydrases I, II, VII, XII, and XIII |
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