目的 合成槲皮素-3-O-乙基苯胺类衍生物并测试其抗肿瘤活性。方法 以槲皮素为先导物,选择性对C环3位羟基进行修饰。以廉价的芦丁为原料,经苄基选择性保护、Williamson 成醚反应,再经 Pd/C 催化加氢脱苄基得到13个槲皮素-3-O-乙基苯胺类衍生物,均未见文献报道,目标产物结构经1H-NMR、13C-NMR、ESI-MS 确证。采用 MTT 法考察了 13 个槲皮素-3-O-乙基苯胺类衍生物对人食管鳞癌(EC109),人胃癌(HGC27),人乳腺癌(MCF-7),小鼠黑色素瘤(B16-F10) 的增殖抑制作用。结果 通过化学方法对槲皮素进行结构修饰后,其体外抗肿瘤活性增强。其中,化合物 5c[IC50值(5.229±0.371) μmol·L-1]、5e[IC50值(2.628±0.087)μmol·L-1]对小鼠黑色素瘤(B16-F10)抑制作用比 5-氟尿嘧啶(5-FU)[IC50值(14.376±0.272)μmol·L-1]好。结论 作为低毒抗黑色素瘤候选物质,化合物5c和5e具有值得进一步研究的价值。
Abstract
OBJECTIVE To synthesize quercetin-3-O-ethylaniline derivatives and test their antitumor activity. METHODS Quercetin was used as the leader to selectively modify the hydroxyl group at the 3-position of the C ring. Using rutin as raw material, after selective protection of benzyl group, Williamson ether formation reaction, and Pd/C catalyzed hydrogenation and debenzylation, 13 quercetin-3-O-ethylaniline derivatives were obtained, all of which have not been reported in the literature. The structures of the target products were confirmed by 1H-NMR, 13C-NMR, and ESI-MS. The MTT method was used to investigate the proliferation inhibitor effects of 13 quercetin-3-O-ethylaniline derivatives on human esophageal squamous cell carcinoma (EC109), human gastric cancer (HGC27), human breast cancer (MCF-7), and mouse melanoma (B16-F10). RESULTS After structural modification of quercetin by chemical methods, the anti-tumor activity in vitro is enhanced. Among them, the inhibitory effects of compound 5c(5.229±0.371) and 5e(2.628±0.087) on mouse melanoma (B16-F10) are better than 5-fluorouracil (5-FU) (14.376±0.272). CONCLUSION Compounds 5c and 5e are worthy of further study as low toxicity anti-melanoma candidates.
关键词
黄酮 /
槲皮素 /
衍生物 /
合成 /
抗肿瘤
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Key words
flavonoid /
quercetin /
derivatives /
synthesis /
antitumor
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中图分类号：
R914.5
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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[2015]70号)
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