Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold
A novel library of human carbonic anhydrase (hCA) inhibitors based on the 2-sulfanilamido[1,2,4]triazolo[1,5-a]pyrimidine skeleton modified at its 7-position was prepared by an efficient convergent procedure. These derivatives were evaluated in vitro for their inhibition properties against a represe...
| 发表在: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Main Authors: | , , , , , , , , , , |
| 格式: | 文件 |
| 语言: | 英语 |
| 出版: |
Taylor & Francis Group
2023-12-01
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| 主题: | |
| 在线阅读: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2270180 |
| _version_ | 1850076039471955968 |
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| author | Romeo Romagnoli Tiziano De Ventura Stefano Manfredini Erika Baldini Claudiu T. Supuran Alessio Nocentini Andrea Brancale Carmine Varricchio Roberta Bortolozzi Lorenzo Manfreda Giampietro Viola |
| author_facet | Romeo Romagnoli Tiziano De Ventura Stefano Manfredini Erika Baldini Claudiu T. Supuran Alessio Nocentini Andrea Brancale Carmine Varricchio Roberta Bortolozzi Lorenzo Manfreda Giampietro Viola |
| author_sort | Romeo Romagnoli |
| collection | DOAJ |
| container_title | Journal of Enzyme Inhibition and Medicinal Chemistry |
| description | A novel library of human carbonic anhydrase (hCA) inhibitors based on the 2-sulfanilamido[1,2,4]triazolo[1,5-a]pyrimidine skeleton modified at its 7-position was prepared by an efficient convergent procedure. These derivatives were evaluated in vitro for their inhibition properties against a representative panel of hCA isoforms (hCA I, II, IV, IX, and XII). The target tumour-associated isoforms hCA IX and XII were potently inhibited with KIs in the low nanomolar range of 5–96 nM and 4–72 nM, respectively. Compounds 1d, 1j, 1v, and 1x were the most potent hCA IX inhibitors with KIs of 5.1, 8.6, 4.7, and 5.1 nM, respectively. Along with derivatives 1d and 1j, compounds 1r and 1ab potently inhibited hCA XII isoform with KIs in a single-digit nanomolar range of 8.8, 5.4, 4.3, and 9.0 nM, respectively. Compounds 1e, 1m, and 1p exhibited the best selectivity against hCA IX and hCA XII isoforms over off-target hCA II, with selectivity indexes ranging from 5 to 14. |
| format | Article |
| id | doaj-art-66ed01ac77d643e097eda1bcaa660cb3 |
| institution | Directory of Open Access Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| spelling | doaj-art-66ed01ac77d643e097eda1bcaa660cb32025-08-20T00:15:30ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2270180Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffoldRomeo Romagnoli0Tiziano De Ventura1Stefano Manfredini2Erika Baldini3Claudiu T. Supuran4Alessio Nocentini5Andrea Brancale6Carmine Varricchio7Roberta Bortolozzi8Lorenzo Manfreda9Giampietro Viola10Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara, ItalyDepartment of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Ferrara, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of Life Sciences and Biotechnology, University of Ferrara, Ferrara, ItalyDepartment of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Florence, ItalyDepartment of NEUROFARBA, Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, Florence, ItalyVysoká Škola Chemicko-Technologická v Praze, Prague, Czech RepublicSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff, UKDepartment of Woman’s and Child’s Health, Hemato-Oncology Lab, University of Padova, Padova, ItalyDepartment of Woman’s and Child’s Health, Hemato-Oncology Lab, University of Padova, Padova, ItalyDepartment of Woman’s and Child’s Health, Hemato-Oncology Lab, University of Padova, Padova, ItalyA novel library of human carbonic anhydrase (hCA) inhibitors based on the 2-sulfanilamido[1,2,4]triazolo[1,5-a]pyrimidine skeleton modified at its 7-position was prepared by an efficient convergent procedure. These derivatives were evaluated in vitro for their inhibition properties against a representative panel of hCA isoforms (hCA I, II, IV, IX, and XII). The target tumour-associated isoforms hCA IX and XII were potently inhibited with KIs in the low nanomolar range of 5–96 nM and 4–72 nM, respectively. Compounds 1d, 1j, 1v, and 1x were the most potent hCA IX inhibitors with KIs of 5.1, 8.6, 4.7, and 5.1 nM, respectively. Along with derivatives 1d and 1j, compounds 1r and 1ab potently inhibited hCA XII isoform with KIs in a single-digit nanomolar range of 8.8, 5.4, 4.3, and 9.0 nM, respectively. Compounds 1e, 1m, and 1p exhibited the best selectivity against hCA IX and hCA XII isoforms over off-target hCA II, with selectivity indexes ranging from 5 to 14.https://www.tandfonline.com/doi/10.1080/14756366.2023.2270180Carbonic anhydrase inhibitorssulphanilamideantiproliferative activity[1,2,4]triazolo[15-a]pyrimidinestructure–activity relationship |
| spellingShingle | Romeo Romagnoli Tiziano De Ventura Stefano Manfredini Erika Baldini Claudiu T. Supuran Alessio Nocentini Andrea Brancale Carmine Varricchio Roberta Bortolozzi Lorenzo Manfreda Giampietro Viola Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold Carbonic anhydrase inhibitors sulphanilamide antiproliferative activity [1,2,4]triazolo[15-a]pyrimidine structure–activity relationship |
| title | Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold |
| title_full | Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold |
| title_fullStr | Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold |
| title_full_unstemmed | Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold |
| title_short | Design, synthesis, and biological investigation of selective human carbonic anhydrase II, IX, and XII inhibitors using 7-aryl/heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold |
| title_sort | design synthesis and biological investigation of selective human carbonic anhydrase ii ix and xii inhibitors using 7 aryl heteroaryl triazolopyrimidines bearing a sulfanilamide scaffold |
| topic | Carbonic anhydrase inhibitors sulphanilamide antiproliferative activity [1,2,4]triazolo[15-a]pyrimidine structure–activity relationship |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2270180 |
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