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目的以天然查尔酮类化合物异甘草素(ILG)为先导物进行结构修饰,制备3-甲氧基异甘草素(3-MO-ILG),并研究ILG与3-MO-ILG的体外抗癌活性。方法利用酸催化的羟醛缩合反应制备ILG与3-MO-ILG目标化合物;应用人肝癌Bel-7402细胞为体外模型,用MTT法观察2种化合物对肝癌细胞增殖的抑制活性;用流式细胞仪测定促Bel-7402细胞凋亡能力;用张氏肝细胞(chang liver)测定对正常细胞的毒性。结果化合物ILG和3-MO-ILG对正常肝细胞无明显毒性,而对肝癌Bel-7402细胞的增殖有一定的抑制活性,浓度在5～200μg/mL范围内,对肝癌Bel-7402细胞的抑制率分别为23.28%～80.01%及41.96%～86.10%;2种化合物对肝癌细胞有明显的促进凋亡作用,最高凋亡率分别可达85%和93.5%。结论人肝癌Bel-7402细胞对甘草查尔酮类化合物具有较高的敏感性;ILG衍生物对人肝癌Bel-7402细胞增殖的抑制活性呈浓度依赖性,而对正常细胞的毒性明显小于对癌细胞的毒性;其抗癌作用机制可能是通过增殖抑制和促进凋亡来产生。本研究为甘草查尔酮类化合物中筛选抗肝癌候选药物奠定一定基础。
OBJECTIVE To construct 3-methoxyisotriginalin (3-MO-ILG) by structurally modifying natural chalcone compound, isoliquiritigenin (ILG), and to study the effect of ILG and 3-MO-ILG in vitro Cancer activity. Methods The target compounds of ILG and 3-MO-ILG were prepared by acid-catalyzed aldol condensation reaction. The inhibitory activity of two compounds on the proliferation of hepatocellular carcinoma cells was evaluated by MTT assay using human hepatoma Bel-7402 cells in vitro. The apoptosis rate of Bel-7402 cells was measured and the toxicity to normal cells was measured with Chang liver cells. Results The compounds ILG and 3-MO-ILG had no obvious toxicity on normal hepatocytes, but inhibited the proliferation of Bel-7402 hepatoma cells at a concentration of 5 ~ 200 μg / mL, which inhibited the growth of Bel-7402 hepatoma cells The rates of apoptosis were 23.28% ~ 80.01% and 41.96% ~ 86.10%, respectively. The two compounds could obviously promote the apoptosis of hepatocellular carcinoma cells with the highest apoptosis rates reaching 85% and 93.5% respectively. CONCLUSION Bel-7402 cells in human hepatocellular carcinoma have a high sensitivity to licochalcone. The inhibitory activity of ILG derivatives on the proliferation of human hepatocellular carcinoma Bel-7402 cells in a concentration-dependent manner is significantly less than that of normal cells Cell toxicity; its anti-cancer mechanism may be through proliferation inhibition and promote apoptosis. This study laid the foundation for the screening of licorice chalcone compounds against liver cancer candidate drugs.