Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction
AbstractHuman DNA topoisomerases are essential for crucial cellular processes, including DNA replication, transcription, chromatin condensation, and maintenance of its structure. One of the significant strategies employed in cancer treatment involves the inhibition of a specific type of topoisomeras...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2302920 |
| _version_ | 1797355135049924608 |
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| author | Mateusz Olszewski Natalia Maciejewska Anoop Kallingal Agnieszka Chylewska Aleksandra M. Dąbrowska Małgorzata Biedulska Mariusz Makowski José M. Padrón Maciej Baginski |
| author_facet | Mateusz Olszewski Natalia Maciejewska Anoop Kallingal Agnieszka Chylewska Aleksandra M. Dąbrowska Małgorzata Biedulska Mariusz Makowski José M. Padrón Maciej Baginski |
| author_sort | Mateusz Olszewski |
| collection | DOAJ |
| description | AbstractHuman DNA topoisomerases are essential for crucial cellular processes, including DNA replication, transcription, chromatin condensation, and maintenance of its structure. One of the significant strategies employed in cancer treatment involves the inhibition of a specific type of topoisomerase, known as topoisomerase II (Topo II). Carbazole derivatives, recognised for their varied biological activities, have recently become a significant focus in oncological research. This study assesses the efficacy of three symmetrically substituted carbazole derivatives: 2,7-Di(2-furyl)-9H-carbazole (27a), 3,6-Di(2-furyl)-9H-carbazole (36a), and 3,6-Di(2-thienyl)-9H-carbazole (36b) – as anticancer agents. Among investigated carbazole derivatives, compound 3,6-di(2-furyl)-9H-carbazole bearing two furan moieties emerged as a novel catalytic inhibitor of Topo II. Notably, 3,6-di(2-furyl)-9H-carbazole effectively selectively inhibited the relaxation and decatenation activities of Topo IIα, with minimal effects on the IIβ isoform. These findings underscore the potential of compound 3,6-Di(2-furyl)-9H-carbazole as a promising lead candidate warranting further investigation in the realm of anticancer drug development. |
| first_indexed | 2024-03-08T13:59:55Z |
| format | Article |
| id | doaj.art-3e3a34c4c647494a825b38608feb0e37 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-03-08T13:59:55Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-3e3a34c4c647494a825b38608feb0e372024-01-15T07:16:58ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2302920Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis inductionMateusz Olszewski0Natalia Maciejewska1Anoop Kallingal2Agnieszka Chylewska3Aleksandra M. Dąbrowska4Małgorzata Biedulska5Mariusz Makowski6José M. Padrón7Maciej Baginski8Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, PolandDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, PolandDepartment of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, PolandDepartment of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, PolandDepartment of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, PolandDepartment of Bioinorganic Chemistry, Faculty of Chemistry, University of Gdansk, Gdansk, PolandBioLab, Instituto Universitario de Bio-Orgánica “Antonio González”, Universidad de La Laguna, La Laguna, SpainDepartment of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, PolandAbstractHuman DNA topoisomerases are essential for crucial cellular processes, including DNA replication, transcription, chromatin condensation, and maintenance of its structure. One of the significant strategies employed in cancer treatment involves the inhibition of a specific type of topoisomerase, known as topoisomerase II (Topo II). Carbazole derivatives, recognised for their varied biological activities, have recently become a significant focus in oncological research. This study assesses the efficacy of three symmetrically substituted carbazole derivatives: 2,7-Di(2-furyl)-9H-carbazole (27a), 3,6-Di(2-furyl)-9H-carbazole (36a), and 3,6-Di(2-thienyl)-9H-carbazole (36b) – as anticancer agents. Among investigated carbazole derivatives, compound 3,6-di(2-furyl)-9H-carbazole bearing two furan moieties emerged as a novel catalytic inhibitor of Topo II. Notably, 3,6-di(2-furyl)-9H-carbazole effectively selectively inhibited the relaxation and decatenation activities of Topo IIα, with minimal effects on the IIβ isoform. These findings underscore the potential of compound 3,6-Di(2-furyl)-9H-carbazole as a promising lead candidate warranting further investigation in the realm of anticancer drug development.https://www.tandfonline.com/doi/10.1080/14756366.2024.2302920Apoptosiscancercarbazoletopoisomerase |
| spellingShingle | Mateusz Olszewski Natalia Maciejewska Anoop Kallingal Agnieszka Chylewska Aleksandra M. Dąbrowska Małgorzata Biedulska Mariusz Makowski José M. Padrón Maciej Baginski Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction Journal of Enzyme Inhibition and Medicinal Chemistry Apoptosis cancer carbazole topoisomerase |
| title | Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction |
| title_full | Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction |
| title_fullStr | Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction |
| title_full_unstemmed | Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction |
| title_short | Palindromic carbazole derivatives: unveiling their antiproliferative effect via topoisomerase II catalytic inhibition and apoptosis induction |
| title_sort | palindromic carbazole derivatives unveiling their antiproliferative effect via topoisomerase ii catalytic inhibition and apoptosis induction |
| topic | Apoptosis cancer carbazole topoisomerase |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2302920 |
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