A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer
Document Type
Article
Publication Date
8-1-2024
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 mu M) against colorectal cancer cells, surpassing 5-fluorouracil (LC50 4.2 mu M). 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. GRAPHICS] .
Keywords
apoptosis, autophagy, chromone, colon cancer, ULK1 inhibitor
Divisions
CHEMISTRY
Funders
Ministry of Higher Education (MOHE) Malaysia (FRGS/1/2022/STG04/UIAM/02/2)
Publication Title
Future Medicinal Chemistry
Volume
16
Issue
15
Publisher
Taylor & Francis
Publisher Location
2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND