目的 合成槲皮素酰胺类衍生物并测定其生物活性。方法 以槲皮素为先导物,选择性对C环3位羟基进行修饰。以芦丁为原料,经苄基选择性保护、Williamson成醚反应,酰胺化反应,再经Pd/C催化加氢脱苄基得到13个槲皮素酰胺类衍生物。采用DPPH法考察了13个目标化合物的抗氧化活性;MTT法考察了13个槲皮素酰胺类衍生物对人食管鳞癌细胞EC109、人食管鳞癌细胞EC9706、人胃癌细胞SGC7901及小鼠黑色素瘤细胞B16-F10的增殖抑制作用。结果 目标产物结构经IR、1H NMR、13C NMR、ESI-MS确证。抗氧化实验显示,大部分目标化合物的SC50小于槲皮素或与槲皮素相当,这提示,3-OH不是槲皮素抗氧化活性的必需基团。抗肿瘤活性实验显示,槲皮素酰胺类衍生物抗肿瘤活性增强,其中,化合物7~13对EC109的抑制作用(IC50=10.25 μmol·L-1)明显优于母药槲皮素(IC50=31.884 μmol·L-1)和5-FU(IC50=41.738 μmol·L-1),是一个很有潜力的新型抗肿瘤候选化合物。结论 通过化学方法对槲皮素进行结构修饰后,抗氧化活性与槲皮素相当,体外抗肿瘤活性显著增强。
Abstract
OBJECTIVE To synthesize the quercetin amide derivatives and determine their biological activities. METHODS Quercetin was used as a precursor whose hydroxyl group on 3-C of C ring was modified selectively. Using rutin as raw material, 13 quercetin amide derivatives were obtained by selective protection of benzyl group, Williamson ether reaction, amidation reaction and Pd/C catalytic hydrodebenzylation. The antioxidant activity of 13 target compounds was investigated by DPPH method. In addation, MTT assay was performed to investigate the proliferation-inhibition effects of these quercetin derivatives on the proliferation of human esophageal carcinoma cell line EC109, human esophageal carcinoma cell line EC9706, human gastric cancer cell line SGC7901 and mouse melanoma cell line B16-F10. RESULTS =The chemical structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and ESI-MS. Antioxidant experiments showed that the values of SC50 of most target compounds were less than or comparable to quercetin, indicating that 3-OH is not an essential group to maintain the antioxidant property of quercetin. Moreover, antitumor activity experiments showed that the anti-tumor activity of quercetin amide derivatives was enhanced. Among them, the inhibition effect of compound 7-13 on EC109 (IC50=10.25 μmol·L-1) was significantly outperformed the parent drug quercetin (IC50=31.884 μmol·L-1) and 5-FU (IC50=41.738 μmol·L-1), which is a very promising novel anti-tumor candidate compound. CONCLUSION After structural modification of quercetin by chemical methods, the antioxidant activity is comparable to that of quercetin, and the antitumor activity in vitro is significantly enhanced.
关键词
黄酮 /
槲皮素 /
酰胺 /
衍生物 /
合成 /
抗氧化 /
抗肿瘤
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Key words
flavonoid /
quercetin /
acidamide /
derivative /
synthesis /
antioxidant /
antitumor
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中图分类号：
R914
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参考文献
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脚注
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基金
郑州市高等学校名师技术技能工作室项目资助(郑教高70号)
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