A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer
Aim: Chromones are promising for anticancer drug development. Methods & results: 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound 8 showed the highest cytotoxicity (LC50 3.2 μM) against colorectal cancer cells, surpassing 5-fluorouracil (LC50 4.2 μM). I...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
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Taylor and Francis Ltd.
2024
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| Online Access: | http://psasir.upm.edu.my/id/eprint/115904/ |
| _version_ | 1848866885733449728 |
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| author | Shamsudin, Nur Farisya Leong, Sze Wei Koeberle, Andreas Suriya, Utid Rungrotmongkol, Thanyada Chia, Suet Lin Taher, Muhammad Haris, Muhammad Salahuddin Alshwyeh, Hussah Abdullah Alosaimi, Areej A Mediani, Ahmed Ilowefah, Muna Abdulsalam Islami, Deri Mohd Faudzi, Siti Munirah Fasihi Mohd Aluwi, Mohd Fadhlizil Wai, Lam Kok Rullah, Kamal |
| author_facet | Shamsudin, Nur Farisya Leong, Sze Wei Koeberle, Andreas Suriya, Utid Rungrotmongkol, Thanyada Chia, Suet Lin Taher, Muhammad Haris, Muhammad Salahuddin Alshwyeh, Hussah Abdullah Alosaimi, Areej A Mediani, Ahmed Ilowefah, Muna Abdulsalam Islami, Deri Mohd Faudzi, Siti Munirah Fasihi Mohd Aluwi, Mohd Fadhlizil Wai, Lam Kok Rullah, Kamal |
| author_sort | Shamsudin, Nur Farisya |
| building | UPM Institutional Repository |
| collection | Online Access |
| description | Aim: Chromones are promising for anticancer drug development. Methods & results: 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound 8 showed the highest cytotoxicity (LC50 3.2 μM) against colorectal cancer cells, surpassing 5-fluorouracil (LC50 4.2 μM). It suppressed colony formation, induced cell cycle arrest and triggered apoptotic cell death, confirmed by staining and apoptosis markers. Cell death was accompanied by enhanced reactive oxygen species formation and modulation of the autophagic machinery (autophagy marker light chain 3B (LC3B); adenosine monophosphate-activated protein kinase (AMPK); protein kinase B (PKB); UNC-51-like kinase (ULK)-1; and ULK2). Molecular docking and dynamic simulations revealed that compound 8 directly binds to ULK1. Conclusion: Compound 8 is a promising lead for autophagy-modulating anti-colon cancer drugs. |
| first_indexed | 2025-11-15T14:27:43Z |
| format | Article |
| id | upm-115904 |
| institution | Universiti Putra Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-15T14:27:43Z |
| publishDate | 2024 |
| publisher | Taylor and Francis Ltd. |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | upm-1159042025-03-14T00:24:30Z http://psasir.upm.edu.my/id/eprint/115904/ A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer Shamsudin, Nur Farisya Leong, Sze Wei Koeberle, Andreas Suriya, Utid Rungrotmongkol, Thanyada Chia, Suet Lin Taher, Muhammad Haris, Muhammad Salahuddin Alshwyeh, Hussah Abdullah Alosaimi, Areej A Mediani, Ahmed Ilowefah, Muna Abdulsalam Islami, Deri Mohd Faudzi, Siti Munirah Fasihi Mohd Aluwi, Mohd Fadhlizil Wai, Lam Kok Rullah, Kamal Aim: Chromones are promising for anticancer drug development. Methods & results: 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound 8 showed the highest cytotoxicity (LC50 3.2 μM) against colorectal cancer cells, surpassing 5-fluorouracil (LC50 4.2 μM). It suppressed colony formation, induced cell cycle arrest and triggered apoptotic cell death, confirmed by staining and apoptosis markers. Cell death was accompanied by enhanced reactive oxygen species formation and modulation of the autophagic machinery (autophagy marker light chain 3B (LC3B); adenosine monophosphate-activated protein kinase (AMPK); protein kinase B (PKB); UNC-51-like kinase (ULK)-1; and ULK2). Molecular docking and dynamic simulations revealed that compound 8 directly binds to ULK1. Conclusion: Compound 8 is a promising lead for autophagy-modulating anti-colon cancer drugs. Taylor and Francis Ltd. 2024 Article PeerReviewed Shamsudin, Nur Farisya and Leong, Sze Wei and Koeberle, Andreas and Suriya, Utid and Rungrotmongkol, Thanyada and Chia, Suet Lin and Taher, Muhammad and Haris, Muhammad Salahuddin and Alshwyeh, Hussah Abdullah and Alosaimi, Areej A and Mediani, Ahmed and Ilowefah, Muna Abdulsalam and Islami, Deri and Mohd Faudzi, Siti Munirah and Fasihi Mohd Aluwi, Mohd Fadhlizil and Wai, Lam Kok and Rullah, Kamal (2024) A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer. Future Medicinal Chemistry, 16 (15). pp. 1499-1517. ISSN 1756-8919; eISSN: 1756-8927 https://www.tandfonline.com/doi/full/10.1080/17568919.2024.2363668 10.1080/17568919.2024.2363668 |
| spellingShingle | Shamsudin, Nur Farisya Leong, Sze Wei Koeberle, Andreas Suriya, Utid Rungrotmongkol, Thanyada Chia, Suet Lin Taher, Muhammad Haris, Muhammad Salahuddin Alshwyeh, Hussah Abdullah Alosaimi, Areej A Mediani, Ahmed Ilowefah, Muna Abdulsalam Islami, Deri Mohd Faudzi, Siti Munirah Fasihi Mohd Aluwi, Mohd Fadhlizil Wai, Lam Kok Rullah, Kamal A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer |
| title | A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer |
| title_full | A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer |
| title_fullStr | A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer |
| title_full_unstemmed | A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer |
| title_short | A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer |
| title_sort | novel chromone-based as a potential inhibitor of ulk1 that modulates autophagy and induces apoptosis in colon cancer |
| url | http://psasir.upm.edu.my/id/eprint/115904/ http://psasir.upm.edu.my/id/eprint/115904/ http://psasir.upm.edu.my/id/eprint/115904/ |