Abstract Some novel 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines have been synthesized from α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,β-unsaturated ketones with guanidine hydrochloride. The purity and structure of the obtained products have been confirmed by thin layer chromatography, IR, 1H NMR, 13C NMR, HSQC, HMBC and MS spectra. All the synthesized of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1-methylquinolin-2(1H)-ones 6a-i were screened for their in vitro cytotoxic activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC50 values equal to 1.33 μM. Compounds 6a-g exhibited weak or insignificant activity with liver cancer cell lines HepG2, while compounds 6a and 6g had more powerful activity in this sequence, with IC50 values equal to 47.99 and 89.38 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that two hydrogen bonding interactions in the binding pocket, as potential ligand binding hot-spot residues for compounds 6b and 6e, may be one of the mechanisms of action responsible for the higher cytotoxic effect on HepG2 and KB cells.

中文翻译：

---

来自 3-乙酰基-4-羟基-1-甲基喹啉-2(1H)-one 的喹啉-嘧啶杂化化合物：合成、细胞毒性、ADMET 和分子对接研究

摘要 以 3-乙酰-4 的 α,β-不饱和酮为原料合成了一些新型 2-氨基-6-芳基-4-(4'-羟基-N-甲基喹啉-2'-on-3'-基)嘧啶。 -羟基-N-甲基喹啉-2-one 通过相应的 α,β-不饱和酮与盐酸胍反应。所得产物的纯度和结构已通过薄层色谱、IR、1H NMR、13C NMR、HSQC、HMBC和MS谱确证。筛选了所有合成的 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1-methylquinolin-2(1H)-ones 6a-i 对人肝细胞癌 HepG2 的体外细胞毒活性和鳞状细胞癌 KB 癌细胞系。化合物 6b 和 6e 在该系列中具有最佳活性，IC50 值等于 1.33 μM。化合物 6a-g 对肝癌细胞系 HepG2 表现出微弱或不显着的活性，而化合物 6a 和 6g 在该序列中具有更强的活性，IC50 值分别等于 47.99 和 89.38 μM。ADMET 特性表明化合物 6b、6e 和 6f 具有药物相似性。交叉对接结果表明，结合口袋中的两个氢键相互作用，作为化合物 6b 和 6e 的潜在配体结合热点残基，可能是导致对 HepG2 和 KB 细胞具有更高细胞毒性作用的作用机制之一。