Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors
In the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic ef...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2023-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2023.2191165 |
| _version_ | 1827123352037228544 |
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| author | Nora Astrain-Redin Niccolò Paoletti Daniel Plano Alessandro Bonardi Paola Gratteri Andrea Angeli Carmen Sanmartin Claudiu T. Supuran |
| author_facet | Nora Astrain-Redin Niccolò Paoletti Daniel Plano Alessandro Bonardi Paola Gratteri Andrea Angeli Carmen Sanmartin Claudiu T. Supuran |
| author_sort | Nora Astrain-Redin |
| collection | DOAJ |
| description | In the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic effects. Selenium-containing compounds, particularly selenols, have been shown to inhibit tumour-associated CA isoforms in the nanomolar range since the properties of the selenium atom favour binding to the active site of the enzyme. In this work, two series of selenoesters (1a–19a and 1b–19b), which gathered NSAIDs, carbo/heterocycles, and fragments from natural products, were evaluated against hCA I, II, IX, and XII. Indomethacin (17b) and flufenamic acid (19b) analogs exhibited selectivity for tumour-associated isoform IX in the low micromolar range. In summary, selenoesters that combine NSAIDs with fragments derived from natural sources have been developed as promising nonclassical inhibitors of the tumour-associated CA isoforms. |
| first_indexed | 2024-03-09T02:02:56Z |
| format | Article |
| id | doaj.art-7da47668284745f78dcb2e9ab0e624ab |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2025-03-20T14:23:33Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7da47668284745f78dcb2e9ab0e624ab2024-09-09T17:23:18ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742023-12-0138110.1080/14756366.2023.2191165Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitorsNora Astrain-Redin0Niccolò Paoletti1Daniel Plano2Alessandro Bonardi3Paola Gratteri4Andrea Angeli5Carmen Sanmartin6Claudiu T. Supuran7Department of Pharmaceutical Technology and Chemistry, University of Navarra, Pamplona, SpainDepartment NEUROFARBA – Pharmaceutical and nutraceutical section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Firenze, Sesto Fiorentino, Florence, ItalyDepartment of Pharmaceutical Technology and Chemistry, University of Navarra, Pamplona, SpainDepartment NEUROFARBA – Pharmaceutical and nutraceutical section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Firenze, Sesto Fiorentino, Florence, ItalyDepartment NEUROFARBA – Pharmaceutical and nutraceutical section, Laboratory of Molecular Modeling Cheminformatics & QSAR, University of Firenze, Sesto Fiorentino, Florence, ItalyDepartment NEUROFARBA – Pharmaceutical and nutraceutical section, University of Firenze, Sesto Fiorentino, Florence, ItalyDepartment of Pharmaceutical Technology and Chemistry, University of Navarra, Pamplona, SpainDepartment NEUROFARBA – Pharmaceutical and nutraceutical section, University of Firenze, Sesto Fiorentino, Florence, ItalyIn the relentless search for new cancer treatments, organoselenium compounds, and carbonic anhydrase (CA) inhibitors have emerged as promising drug candidates. CA isoforms IX and XII are overexpressed in many types of cancer, and their inhibition is associated with potent antitumor/antimetastatic effects. Selenium-containing compounds, particularly selenols, have been shown to inhibit tumour-associated CA isoforms in the nanomolar range since the properties of the selenium atom favour binding to the active site of the enzyme. In this work, two series of selenoesters (1a–19a and 1b–19b), which gathered NSAIDs, carbo/heterocycles, and fragments from natural products, were evaluated against hCA I, II, IX, and XII. Indomethacin (17b) and flufenamic acid (19b) analogs exhibited selectivity for tumour-associated isoform IX in the low micromolar range. In summary, selenoesters that combine NSAIDs with fragments derived from natural sources have been developed as promising nonclassical inhibitors of the tumour-associated CA isoforms.https://www.tandfonline.com/doi/10.1080/14756366.2023.2191165Seleniumcarbonic anhydraseinhibitorsNSAIDstumours |
| spellingShingle | Nora Astrain-Redin Niccolò Paoletti Daniel Plano Alessandro Bonardi Paola Gratteri Andrea Angeli Carmen Sanmartin Claudiu T. Supuran Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry Selenium carbonic anhydrase inhibitors NSAIDs tumours |
| title | Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors |
| title_full | Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors |
| title_fullStr | Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors |
| title_full_unstemmed | Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors |
| title_short | Selenium-analogs based on natural sources as cancer-associated carbonic anhydrase isoforms IX and XII inhibitors |
| title_sort | selenium analogs based on natural sources as cancer associated carbonic anhydrase isoforms ix and xii inhibitors |
| topic | Selenium carbonic anhydrase inhibitors NSAIDs tumours |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2023.2191165 |
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