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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[Box: see text].
摘要：
目的：色原在抗癌药物开发中具有广阔的应用前景。方法和结果：合成了12个基于色酮的化合物，并对癌细胞系进行了测试。化合物8对结肠直肠癌细胞显示出最高的细胞毒性(LC50为3.2μM),超过5-氟尿嘧啶（LC504.2μM）。它抑制了菌落的形成，诱导细胞周期停滞和触发凋亡细胞死亡，通过染色和凋亡标志物证实。细胞死亡伴随着增强的活性氧形成和自噬机制的调节(自噬标记轻链3B(LC3B);一磷酸腺苷活化蛋白激酶(AMPK);蛋白激酶B(PKB);UNC-51样激酶(ULK)-1;和ULK2)。分子对接和动态模拟显示化合物8直接结合ULK1。结论：化合物8是一种有前途的自噬调节抗结肠癌药物。
[方框：见正文]。
[方框：见正文]。
