Antischistosomal tetrahydro-γ-carboline sulfonamides
[Display omitted] We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antis...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry letters 2022-03, Vol.59, p.128546-128546, Article 128546 |
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| container_end_page | 128546 |
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| container_title | Bioorganic & medicinal chemistry letters |
| container_volume | 59 |
| creator | Ren, Rongguo Wang, Xiaofang Leas, Derek A. Häberli, Cécile Cal, Monica Dong, Yuxiang Kaiser, Marcel Keiser, Jennifer Vennerstrom, Jonathan L. |
| description | [Display omitted]
We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC50 values |
| doi_str_mv | 10.1016/j.bmcl.2022.128546 |
| format | Article |
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We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC50 values <5 µM against ex vivo Schistosoma mansoni.</description><identifier>ISSN: 0960-894X</identifier><identifier>EISSN: 1464-3405</identifier><identifier>DOI: 10.1016/j.bmcl.2022.128546</identifier><identifier>PMID: 35031451</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Antischistosomal ; Carbolines - chemical synthesis ; Carbolines - chemistry ; Carbolines - pharmacology ; Dose-Response Relationship, Drug ; Molecular Structure ; SAR ; Schistosoma mansoni - drug effects ; Structure-Activity Relationship ; Sulfonamides ; Sulfonamides - chemical synthesis ; Sulfonamides - chemistry ; Sulfonamides - pharmacology ; Tetrahydro-γ-carboline</subject><ispartof>Bioorganic & medicinal chemistry letters, 2022-03, Vol.59, p.128546-128546, Article 128546</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-d37a4e92168874dbe6e886330d2a07f5a3e22b380fa340211bb25c25125fb7653</citedby><cites>FETCH-LOGICAL-c455t-d37a4e92168874dbe6e886330d2a07f5a3e22b380fa340211bb25c25125fb7653</cites><orcidid>0000-0003-0075-2336 ; 0000-0002-1738-1212 ; 0000-0002-0190-543X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmcl.2022.128546$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,780,784,885,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35031451$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ren, Rongguo</creatorcontrib><creatorcontrib>Wang, Xiaofang</creatorcontrib><creatorcontrib>Leas, Derek A.</creatorcontrib><creatorcontrib>Häberli, Cécile</creatorcontrib><creatorcontrib>Cal, Monica</creatorcontrib><creatorcontrib>Dong, Yuxiang</creatorcontrib><creatorcontrib>Kaiser, Marcel</creatorcontrib><creatorcontrib>Keiser, Jennifer</creatorcontrib><creatorcontrib>Vennerstrom, Jonathan L.</creatorcontrib><title>Antischistosomal tetrahydro-γ-carboline sulfonamides</title><title>Bioorganic & medicinal chemistry letters</title><addtitle>Bioorg Med Chem Lett</addtitle><description>[Display omitted]
We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC50 values <5 µM against ex vivo Schistosoma mansoni.</description><subject>Animals</subject><subject>Antischistosomal</subject><subject>Carbolines - chemical synthesis</subject><subject>Carbolines - chemistry</subject><subject>Carbolines - pharmacology</subject><subject>Dose-Response Relationship, Drug</subject><subject>Molecular Structure</subject><subject>SAR</subject><subject>Schistosoma mansoni - drug effects</subject><subject>Structure-Activity Relationship</subject><subject>Sulfonamides</subject><subject>Sulfonamides - chemical synthesis</subject><subject>Sulfonamides - chemistry</subject><subject>Sulfonamides - pharmacology</subject><subject>Tetrahydro-γ-carboline</subject><issn>0960-894X</issn><issn>1464-3405</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1Kw0AUhQdRbK2-gAvpCyTOfyYgQin-QcGNgrth_mKnJJkykxb6XL6Hz2RKtOjG1V3cc8499wPgEsEcQcSvV7luTJ1jiHGOsGCUH4ExopxmhEJ2DMaw5DATJX0bgbOUVhAiCik9BSPCIEGUoTFgs7bzySx96kIKjaqnneuiWu5sDNnnR2ZU1KH2rZumTV2FVjXeunQOTipVJ3fxPSfg9f7uZf6YLZ4fnuazRWYoY11mSaGoKzHiQhTUasedEJwQaLGCRcUUcRhrImCl-sYYIa0xM5ghzCpdcEYm4HbIXW9046xxbd-tluvoGxV3Migv_25av5TvYSuFwJyVsA_AQ4CJIaXoqoMXQbmHKFdyD1HuIcoBYm-6-n31YPmh1gtuBoHrf996F2Uy3rXGWR-d6aQN_r_8Lw-YhNI</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Ren, Rongguo</creator><creator>Wang, Xiaofang</creator><creator>Leas, Derek A.</creator><creator>Häberli, Cécile</creator><creator>Cal, Monica</creator><creator>Dong, Yuxiang</creator><creator>Kaiser, Marcel</creator><creator>Keiser, Jennifer</creator><creator>Vennerstrom, Jonathan L.</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>5PM</scope><orcidid>https://orcid.org/0000-0003-0075-2336</orcidid><orcidid>https://orcid.org/0000-0002-1738-1212</orcidid><orcidid>https://orcid.org/0000-0002-0190-543X</orcidid></search><sort><creationdate>20220301</creationdate><title>Antischistosomal tetrahydro-γ-carboline sulfonamides</title><author>Ren, Rongguo ; Wang, Xiaofang ; Leas, Derek A. ; Häberli, Cécile ; Cal, Monica ; Dong, Yuxiang ; Kaiser, Marcel ; Keiser, Jennifer ; Vennerstrom, Jonathan L.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c455t-d37a4e92168874dbe6e886330d2a07f5a3e22b380fa340211bb25c25125fb7653</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Antischistosomal</topic><topic>Carbolines - chemical synthesis</topic><topic>Carbolines - chemistry</topic><topic>Carbolines - pharmacology</topic><topic>Dose-Response Relationship, Drug</topic><topic>Molecular Structure</topic><topic>SAR</topic><topic>Schistosoma mansoni - drug effects</topic><topic>Structure-Activity Relationship</topic><topic>Sulfonamides</topic><topic>Sulfonamides - chemical synthesis</topic><topic>Sulfonamides - chemistry</topic><topic>Sulfonamides - pharmacology</topic><topic>Tetrahydro-γ-carboline</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ren, Rongguo</creatorcontrib><creatorcontrib>Wang, Xiaofang</creatorcontrib><creatorcontrib>Leas, Derek A.</creatorcontrib><creatorcontrib>Häberli, Cécile</creatorcontrib><creatorcontrib>Cal, Monica</creatorcontrib><creatorcontrib>Dong, Yuxiang</creatorcontrib><creatorcontrib>Kaiser, Marcel</creatorcontrib><creatorcontrib>Keiser, Jennifer</creatorcontrib><creatorcontrib>Vennerstrom, Jonathan L.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Bioorganic & medicinal chemistry letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ren, Rongguo</au><au>Wang, Xiaofang</au><au>Leas, Derek A.</au><au>Häberli, Cécile</au><au>Cal, Monica</au><au>Dong, Yuxiang</au><au>Kaiser, Marcel</au><au>Keiser, Jennifer</au><au>Vennerstrom, Jonathan L.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antischistosomal tetrahydro-γ-carboline sulfonamides</atitle><jtitle>Bioorganic & medicinal chemistry letters</jtitle><addtitle>Bioorg Med Chem Lett</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>59</volume><spage>128546</spage><epage>128546</epage><pages>128546-128546</pages><artnum>128546</artnum><issn>0960-894X</issn><eissn>1464-3405</eissn><abstract>[Display omitted]
We discovered tetrahydro-γ-carboline sulfonamides as a new antischistosomal chemotype. The aryl sulfonamide and tetrahydro-γ-carboline substructures were required for high antischistosomal activity. Increasing polarity improved solubility and metabolic stability but decreased antischistosomal activity. We identified two compounds with IC50 values <5 µM against ex vivo Schistosoma mansoni.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>35031451</pmid><doi>10.1016/j.bmcl.2022.128546</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-0075-2336</orcidid><orcidid>https://orcid.org/0000-0002-1738-1212</orcidid><orcidid>https://orcid.org/0000-0002-0190-543X</orcidid><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 0960-894X |
| ispartof | Bioorganic & medicinal chemistry letters, 2022-03, Vol.59, p.128546-128546, Article 128546 |
| issn | 0960-894X 1464-3405 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Animals Antischistosomal Carbolines - chemical synthesis Carbolines - chemistry Carbolines - pharmacology Dose-Response Relationship, Drug Molecular Structure SAR Schistosoma mansoni - drug effects Structure-Activity Relationship Sulfonamides Sulfonamides - chemical synthesis Sulfonamides - chemistry Sulfonamides - pharmacology Tetrahydro-γ-carboline |
| title | Antischistosomal tetrahydro-γ-carboline sulfonamides |
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