A Novel Chromone-based As a Potential Inhibitor of ULK1 That Modulates Autophagy and Induces Apoptosis in Colon Cancer

Overview

Journal Future Med Chem

Specialties Chemistry
Pharmacy

Date 2024 Jul 1

PMID 38949858

Authors

Nur Farisya Shamsudin

Sze-Wei Leong

Andreas Koeberle

Utid Suriya

Thanyada Rungrotmongkol

Suet Lin Chia

Muhammad Taher

Muhammad Salahuddin Haris

Hussah Abdullah Alshwyeh

Areej A Alosaimi

Ahmed Mediani

Muna Abdulsalam Ilowefah

Deri Islami

Siti Munirah Mohd Faudzi

Mohd Fadhlizil Fasihi Mohd Aluwi

Lam Kok Wai

Kamal Rullah

Affiliations

Soon will be listed here.

Abstract

Chromones are promising for anticancer drug development. 12 chromone-based compounds were synthesized and tested against cancer cell lines. Compound showed the highest cytotoxicity (LC 3.2 μM) against colorectal cancer cells, surpassing 5-fluorouracil (LC 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 directly binds to ULK1. Compound is a promising lead for autophagy-modulating anti-colon cancer drugs.

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