TY - JOUR
T1 - A novel chromone-based as a potential inhibitor of ULK1 that modulates autophagy and induces apoptosis in colon cancer
AU - Shamsudin, Nur Farisya
AU - Leong, Sze Wei
AU - Koeberle, Andreas
AU - Suriya, Utid
AU - Rungrotmongkol, Thanyada
AU - Chia, Suet Lin
AU - Taher, Muhammad
AU - Haris, Muhammad Salahuddin
AU - Alshwyeh, Hussah Abdullah
AU - Alosaimi, Areej A.
AU - Mediani, Ahmed
AU - Ilowefah, Muna Abdulsalam
AU - Islami, Deri
AU - Mohd Faudzi, Siti Munirah
AU - Fasihi Mohd Aluwi, Mohd Fadhlizil
AU - Wai, Lam Kok
AU - Rullah, Kamal
N1 - Publisher Copyright:
© 2024 Informa UK Limited, trading as Taylor & Francis Group.
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
KW - ULK1 inhibitor
KW - apoptosis
KW - autophagy
KW - chromone
KW - colon cancer
UR - http://www.scopus.com/inward/record.url?scp=85197645904&partnerID=8YFLogxK
U2 - 10.1080/17568919.2024.2363668
DO - 10.1080/17568919.2024.2363668
M3 - Article
AN - SCOPUS:85197645904
SN - 1756-8919
VL - 16
SP - 1499
EP - 1517
JO - Future Medicinal Chemistry
JF - Future Medicinal Chemistry
IS - 15
ER -