槲皮素-3-O-乙基苯胺类衍生物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activities of Quercetin-3-O-Ethylaniline Derivatives

作　　者：邵香敏 从洋 孟凡华 颜子童[2] 翟广玉 SHAO Xiang-min;CONG Yang;MENG Fan-hua;YAN Zi-tong;ZHAI Guang-yu(School of Pharmacy and Chemical Engineering,Zhengzhou University of Industrial Technology,Zhengzhou 451100,China;School of Pharmacy,Zhengzhou University,Zhengzhou 450001,China)

机构地区：[1]郑州工业应用技术学院药学与化学工程学院,郑州451100 [2]郑州大学药学院,郑州450001

出　　处：《中国药学杂志》2023年第10期884-890,共7页Chinese Pharmaceutical Journal

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)。

摘　　要：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。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 

分 类 号：R914.5[医药卫生—药物化学]