Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII
KI (hCA I)=7.6nM; KI (hCA II)=65nM, KI (hCA IX)=8.3nM; KI (hCA XII)=9.5nM. A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatize...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2009-06, Vol.19 (11), p.2931-2934 |
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| container_title | Bioorganic & medicinal chemistry letters |
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| creator | Güzel, Özlen Maresca, Alfonso Scozzafava, Andrea Salman, Aydın Balaban, Alexandru T. Supuran, Claudiu T. |
| description | KI (hCA I)=7.6nM; KI (hCA II)=65nM, KI (hCA IX)=8.3nM; KI (hCA XII)=9.5nM.
A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents. |
| doi_str_mv | 10.1016/j.bmcl.2009.04.068 |
| format | Article |
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A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2009.04.068</identifier><identifier>PMID: 19410461</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>Antigens, Neoplasm - chemistry ; Antigens, Neoplasm - metabolism ; Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antitumor agent ; Biological and medical sciences ; CA IX ; CA XII ; Carbonic anhydrase ; Carbonic Anhydrase Inhibitors - chemical synthesis ; Carbonic Anhydrase Inhibitors - chemistry ; Carbonic Anhydrase Inhibitors - pharmacology ; Carbonic Anhydrase IX ; Carbonic Anhydrases - chemistry ; Carbonic Anhydrases - metabolism ; General aspects ; Humans ; Medical sciences ; Pharmacology. Drug treatments ; Pyridinium Compounds - chemical synthesis ; Pyridinium Compounds - chemistry ; Pyridinium Compounds - pharmacology ; Pyridinium salt ; Sulfonamide ; Sulfonamides - chemical synthesis ; Sulfonamides - chemistry ; Sulfonamides - pharmacology ; Tumor-associated isoform</subject><ispartof>Bioorganic & medicinal chemistry letters, 2009-06, Vol.19 (11), p.2931-2934</ispartof><rights>2009 Elsevier Ltd</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c415t-daeca88c95dec779a6e86f72585913ac62ed173169b57fc02403b1f6c4382a2e3</citedby><cites>FETCH-LOGICAL-c415t-daeca88c95dec779a6e86f72585913ac62ed173169b57fc02403b1f6c4382a2e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0960894X09005769$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,65309</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21510588$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19410461$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Güzel, Özlen</creatorcontrib><creatorcontrib>Maresca, Alfonso</creatorcontrib><creatorcontrib>Scozzafava, Andrea</creatorcontrib><creatorcontrib>Salman, Aydın</creatorcontrib><creatorcontrib>Balaban, Alexandru T.</creatorcontrib><creatorcontrib>Supuran, Claudiu T.</creatorcontrib><title>Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>KI (hCA I)=7.6nM; KI (hCA II)=65nM, KI (hCA IX)=8.3nM; KI (hCA XII)=9.5nM.
A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents.</description><subject>Antigens, Neoplasm - chemistry</subject><subject>Antigens, Neoplasm - metabolism</subject><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antitumor agent</subject><subject>Biological and medical sciences</subject><subject>CA IX</subject><subject>CA XII</subject><subject>Carbonic anhydrase</subject><subject>Carbonic Anhydrase Inhibitors - chemical synthesis</subject><subject>Carbonic Anhydrase Inhibitors - chemistry</subject><subject>Carbonic Anhydrase Inhibitors - pharmacology</subject><subject>Carbonic Anhydrase IX</subject><subject>Carbonic Anhydrases - chemistry</subject><subject>Carbonic Anhydrases - metabolism</subject><subject>General aspects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Pharmacology. Drug treatments</subject><subject>Pyridinium Compounds - chemical synthesis</subject><subject>Pyridinium Compounds - chemistry</subject><subject>Pyridinium Compounds - pharmacology</subject><subject>Pyridinium salt</subject><subject>Sulfonamide</subject><subject>Sulfonamides - chemical synthesis</subject><subject>Sulfonamides - chemistry</subject><subject>Sulfonamides - pharmacology</subject><subject>Tumor-associated isoform</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUGL1DAcxYso7rr6BTxILorCpiZpmrawFxnUHVjwoMLcQpr862RokzFJB-q39BuZ2RnUk55y-b33f3mvKJ5TUlJCxdtd2U96LBkhXUl4SUT7oLikXHBccVI_LC5JJwhuO765KJ7EuCOEcsL54-KCdpwSLuhl8XOlQu-d1Ui57WKCioCs29reJh9iiT4vLm0h2oj8gNg1vxY4BTtB2i7jfgnWWGfnCRkI9qCSPcAJxK_vzX5Y5_X9gWV8gyuswjJieoutM34EXOM4j4N3arImC5VO1n1DKqK9T-DSX0GOpjkHSvPkA1Yxem1VAoNs9IMPE1pv8gcM2qzXT4tHgxojPDu_V8XXD--_rG7x3aeP69W7O6w5rRM2CrRqW93VBnTTdEpAK4aG1W3d0UppwcDQpqKi6-tm0IRxUvV0EJpXLVMMqqvi1cl3H_z3GWKSk40axlE58HOUomFV23TsvyAjghBG6wyyE6iDjzHAIPe56tyZpEQeF5c7eVxcHheXhMu8eBa9OLvP_QTmj-Q8cQZengEVtRqHoJy28TeXD1NSt0ejmxMHubSDhSCjtuA0GBtAJ2m8_VeOX_CdzXU</recordid><startdate>20090601</startdate><enddate>20090601</enddate><creator>Güzel, Özlen</creator><creator>Maresca, Alfonso</creator><creator>Scozzafava, Andrea</creator><creator>Salman, Aydın</creator><creator>Balaban, Alexandru T.</creator><creator>Supuran, Claudiu T.</creator><general>Elsevier Ltd</general><general>Elsevier</general><scope>IQODW</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>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20090601</creationdate><title>Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII</title><author>Güzel, Özlen ; Maresca, Alfonso ; Scozzafava, Andrea ; Salman, Aydın ; Balaban, Alexandru T. ; Supuran, Claudiu T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c415t-daeca88c95dec779a6e86f72585913ac62ed173169b57fc02403b1f6c4382a2e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Antigens, Neoplasm - chemistry</topic><topic>Antigens, Neoplasm - metabolism</topic><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antitumor agent</topic><topic>Biological and medical sciences</topic><topic>CA IX</topic><topic>CA XII</topic><topic>Carbonic anhydrase</topic><topic>Carbonic Anhydrase Inhibitors - chemical synthesis</topic><topic>Carbonic Anhydrase Inhibitors - chemistry</topic><topic>Carbonic Anhydrase Inhibitors - pharmacology</topic><topic>Carbonic Anhydrase IX</topic><topic>Carbonic Anhydrases - chemistry</topic><topic>Carbonic Anhydrases - metabolism</topic><topic>General aspects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Pharmacology. Drug treatments</topic><topic>Pyridinium Compounds - chemical synthesis</topic><topic>Pyridinium Compounds - chemistry</topic><topic>Pyridinium Compounds - pharmacology</topic><topic>Pyridinium salt</topic><topic>Sulfonamide</topic><topic>Sulfonamides - chemical synthesis</topic><topic>Sulfonamides - chemistry</topic><topic>Sulfonamides - pharmacology</topic><topic>Tumor-associated isoform</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Güzel, Özlen</creatorcontrib><creatorcontrib>Maresca, Alfonso</creatorcontrib><creatorcontrib>Scozzafava, Andrea</creatorcontrib><creatorcontrib>Salman, Aydın</creatorcontrib><creatorcontrib>Balaban, Alexandru T.</creatorcontrib><creatorcontrib>Supuran, Claudiu T.</creatorcontrib><collection>Pascal-Francis</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>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Güzel, Özlen</au><au>Maresca, Alfonso</au><au>Scozzafava, Andrea</au><au>Salman, Aydın</au><au>Balaban, Alexandru T.</au><au>Supuran, Claudiu T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2009-06-01</date><risdate>2009</risdate><volume>19</volume><issue>11</issue><spage>2931</spage><epage>2934</epage><pages>2931-2934</pages><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>KI (hCA I)=7.6nM; KI (hCA II)=65nM, KI (hCA IX)=8.3nM; KI (hCA XII)=9.5nM.
A series of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4- substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, or a perfluorophenyl moiety, has been derivatized by reaction with 2,4,6-trimethylpyrylium perchlorate. The new sulfonamides were evaluated as inhibitors of four mammalian carbonic anhydrase (CA, EC 4.2.1.1) isoforms, that is, CA I, II (cytosolic), CA IX and XII (transmembrane, tumor-associated forms). Excellent inhibitory activity was observed against hCA IX with most of these sulfonamides, and against hCA XII with some of the new compounds. These compounds were generally less effective inhibitors of hCA II. Being membrane impermeant, these positively-charged sulfonamides are interesting candidates for targeting the tumor-associated CA IX and XII, as possible diagnostic tools or therapeutic agents.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>19410461</pmid><doi>10.1016/j.bmcl.2009.04.068</doi><tpages>4</tpages></addata></record> |
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| identifier | ISSN: 0960-894X |
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| language | eng |
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| subjects | Antigens, Neoplasm - chemistry Antigens, Neoplasm - metabolism Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antitumor agent Biological and medical sciences CA IX CA XII Carbonic anhydrase Carbonic Anhydrase Inhibitors - chemical synthesis Carbonic Anhydrase Inhibitors - chemistry Carbonic Anhydrase Inhibitors - pharmacology Carbonic Anhydrase IX Carbonic Anhydrases - chemistry Carbonic Anhydrases - metabolism General aspects Humans Medical sciences Pharmacology. Drug treatments Pyridinium Compounds - chemical synthesis Pyridinium Compounds - chemistry Pyridinium Compounds - pharmacology Pyridinium salt Sulfonamide Sulfonamides - chemical synthesis Sulfonamides - chemistry Sulfonamides - pharmacology Tumor-associated isoform |
| title | Carbonic anhydrase inhibitors. Synthesis of 2,4,6-trimethylpyridinium derivatives of 2-(hydrazinocarbonyl)-3-aryl-1H-indole-5-sulfonamides acting as potent inhibitors of the tumor-associated isoform IX and XII |
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