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目的设计并合成新型具有抗肿瘤活性的2-苯氨基咪唑啉-5-酮类化合物。方法以甘氨酸为起始原料,经环合、Knoevenagel缩合、N-烷基化、S-烷基化、取代5步反应合成2-苯氨基咪唑啉-5-酮类衍生物,并初步考察目标物对H460(人肺癌细胞)、HT29(人结肠癌细胞)以及A549(非小细胞肺癌细胞)的增殖抑制活性。结果与结论合成了11个未见文献报道的2-苯氨基咪唑啉-5-酮衍生物,化合物的结构经~1H-NMR、MS谱确证。体外活性测试结果显示,化合物1c、1e表现出较强的抑制细胞增殖活性,其对试验的3种肿瘤细胞的IC_(50)值分别为0.41、0.38(H460),0.41、0.66(HT29),1.44、0.75(A549)μmol·L~(-1),阳性对照药物顺铂(cisplatin)对3种肿瘤细胞的IC50值分别为0.22、0.62、0.35μmol·L~(-1)。初步探讨了目标化合物的构效关系,为进一步结构改造提供参考。
Objective To design and synthesize 2-anilinoimidazolin-5-ones with antitumor activity. Methods Glycine was used as the starting material to synthesize 2-anilinoimidazolin-5-one derivatives by ring-closure, Knoevenagel condensation, N-alkylation and S-alkylation, H460 (human lung cancer cells), HT29 (human colon cancer cells), and A549 (non-small cell lung cancer cells). RESULTS AND CONCLUSION Eleven novel 2-anilinoimidazol-5-one derivatives were synthesized. The structures of the compounds were confirmed by ~ 1H-NMR and MS spectra. In vitro activity test showed that compounds 1c and 1e showed strong inhibitory activity on cell proliferation. The IC 50 values of the three tumor cells were 0.41,0.38 (H460), 0.41,0.66 (HT29) 1.44, 0.75 (A549) μmol·L -1. The IC50 values of the positive control drug cisplatin on the three tumor cells were 0.22,0.62,0.35μmol·L -1, respectively. The structure-activity relationship of the target compounds is discussed preliminarily, which provides a reference for further structural transformation.