Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases
Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds 5, 4b, and 4a possessed potent cytotoxic activity against PC-3 cells with IC50 3.56, 8.99, and 10.22 µM, respectively. Compound 4c displayed cytotoxicity more tha...
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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/10.1080/14756366.2024.2311157 |
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| author | Lina M. A. Abdel Ghany Tarek S. Ibrahim Abdulrahman S. Alharbi Mohamed S. Abdel-Aziz Eman M. El-labbad Mohamed Elagawany Noha Ryad |
| author_facet | Lina M. A. Abdel Ghany Tarek S. Ibrahim Abdulrahman S. Alharbi Mohamed S. Abdel-Aziz Eman M. El-labbad Mohamed Elagawany Noha Ryad |
| author_sort | Lina M. A. Abdel Ghany |
| collection | DOAJ |
| description | Novel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds 5, 4b, and 4a possessed potent cytotoxic activity against PC-3 cells with IC50 3.56, 8.99, and 10.22 µM, respectively. Compound 4c displayed cytotoxicity more than erlotinib in the MDA-MB-231 cells with IC50 8.5 µM. Moreover, compound 5 exhibited potent inhibitory activity on EFGR with IC50 0.1812 µM, as well as PI3Kβ inhibitory activity that was twofold higher than LY294002, suggesting that this compound has a dual EGFR and PI3Kβ inhibiting activity. Docking aligns with the in vitro results and sheds light on the molecular mechanisms underlying dual targeting. Furthermore, compound 5 decreased AKT and m-TOR expression in PC-3 cells, showing that it specifically targets these cells via the EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, compound 5 caused cell cycle arrest at S phase and induced activation of both intrinsic and extrinsic apoptotic pathways. |
| format | Article |
| id | doaj-art-88741326acc1429f93baf6db565203f9 |
| institution | OA Journals |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-88741326acc1429f93baf6db565203f92025-08-20T02:35:33ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2311157Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinasesLina M. A. Abdel Ghany0Tarek S. Ibrahim1Abdulrahman S. Alharbi2Mohamed S. Abdel-Aziz3Eman M. El-labbad4Mohamed Elagawany5Noha Ryad6Pharmaceutical Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza, EgyptDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi ArabiaDepartment of Chemistry, College of Science and Humanities-Dawadmi, Shaqra University, Sajir, Saudi ArabiaMicrobial Chemistry Department, Biotechnology Research Institute, National Research Centre, Cairo, EgyptDepartment of Pharmaceutical Sciences, College of Pharmacy, Gulf Medical University, Ajman, United Arab EmiratesDepartment of Pharmaceutical Chemistry, Damanhour University, Damanhour, Buhaira, EgyptPharmaceutical Organic Chemistry Department, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology, 6th of October City, Giza, EgyptNovel coumarin derivatives were synthesised and tested for their cytotoxicity against human cancer cells (PC-3 and MDA-MB-231). Compounds 5, 4b, and 4a possessed potent cytotoxic activity against PC-3 cells with IC50 3.56, 8.99, and 10.22 µM, respectively. Compound 4c displayed cytotoxicity more than erlotinib in the MDA-MB-231 cells with IC50 8.5 µM. Moreover, compound 5 exhibited potent inhibitory activity on EFGR with IC50 0.1812 µM, as well as PI3Kβ inhibitory activity that was twofold higher than LY294002, suggesting that this compound has a dual EGFR and PI3Kβ inhibiting activity. Docking aligns with the in vitro results and sheds light on the molecular mechanisms underlying dual targeting. Furthermore, compound 5 decreased AKT and m-TOR expression in PC-3 cells, showing that it specifically targets these cells via the EGFR/PI3K/Akt/m-TOR signalling pathway. Simultaneously, compound 5 caused cell cycle arrest at S phase and induced activation of both intrinsic and extrinsic apoptotic pathways.https://www.tandfonline.com/doi/10.1080/14756366.2024.2311157CoumarinsPC-3cytotoxicityapoptosisdocking |
| spellingShingle | Lina M. A. Abdel Ghany Tarek S. Ibrahim Abdulrahman S. Alharbi Mohamed S. Abdel-Aziz Eman M. El-labbad Mohamed Elagawany Noha Ryad Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases Journal of Enzyme Inhibition and Medicinal Chemistry Coumarins PC-3 cytotoxicity apoptosis docking |
| title | Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases |
| title_full | Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases |
| title_fullStr | Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases |
| title_full_unstemmed | Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases |
| title_short | Development of certain benzylidene coumarin derivatives as anti-prostate cancer agents targeting EGFR and PI3Kβ kinases |
| title_sort | development of certain benzylidene coumarin derivatives as anti prostate cancer agents targeting egfr and pi3kβ kinases |
| topic | Coumarins PC-3 cytotoxicity apoptosis docking |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2311157 |
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