A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer

Citation

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

Abstract

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.

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Additional Metadata

Item Type:	Article
Divisions:	Institute of Bioscience
DOI Number:	https://doi.org/10.1080/17568919.2024.2363668
Publisher:	Taylor and Francis Ltd.
Keywords:	Apoptosis; Autophagy; Chromone; Colon cancer; ULK1 inhibitor
Depositing User:	Ms. Che Wa Zakaria
Date Deposited:	14 Mar 2025 00:24
Last Modified:	14 Mar 2025 00:24
Altmetrics:	http://www.altmetric.com/details.php?domain=psasir.upm.edu.my&doi=10.1080/17568919.2024.2363668
URI:	http://psasir.upm.edu.my/id/eprint/115904
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