槲皮素8位取代衍生物的合成与抑制肿瘤细胞增殖活性评价  

Synthesis and cytotoxic activity evaluation of 8-substituted quercetin derivatives

作　　者：程严 丁颖 张佳伟 全德武 李明媛 滕玉鸥[1] 郁彭[1] CHENG Yan;DING Ying;ZHANG Jia-wei;QUAN De-wu;LI Ming-yuan;TENG Yu-ou;YU Peng(China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry,Tianjin University of Science and Technology,Tianjin 300457,China)

机构地区：[1]天津科技大学,食品营养与安全和药物化学国家国际科技合作基地,天津300457

出　　处：《国际药学研究杂志》2020年第6期430-435,共6页Journal of International Pharmaceutical Research

摘　　要：目的设计合成8位不同取代的槲皮素衍生物,并进行构效关系分析,以发现新的具有体外抑制肿瘤细胞增殖活性的槲皮素类先导物。方法以芦丁为起始原料,通过酸水解制得槲皮素,再经对槲皮素的羟基全保护和卤代反应、以及Suzuki-coupling或Heck-coupling反应,得到8位取代的目标化合物3a^3h,采用MTT法评价目标化合物的体外抑制肿瘤细胞增殖活性。结果与结论合成了8个未见文献报道的目标化合物,结构经1H NMR、13C NMR和MS确证。其中,化合物3b^3h对HepG2细胞、3b和3d对HT-29细胞、3b^3d和3f^3h对K562细胞的抑制活性较槲皮素均显著增强,研究结果提示了有益的构效关系初步规律。Objective To synthesize 8-substituted quercetin derivatives and test their cytotoxicity on human cancer cell lines,so as to find out hit or lead compounds via structure activity relationship(SAR)analysis.Methods Using rutin as the raw material,quercetin was obtained by the acid hydrolysis of rutin,and the 8-substituted quercetin derivatives,3a-3h,were synthesized via the whole hydroxyl protection of quercetin and then halogenation,followed by the Suzuki coupling or heck coupling reaction.The in vitro inhibitory activity of these derivatives was assayed by the MTT method using human cancer HepG2,HT-29 and K562 cell lines.Results and Conclusion Eight new target compounds,3a-3h,were synthesized,and their structures were confirmed by the 1H NMR,13C NMR and MS data.The inhibitory effect of 3b-3h on HepG2 cell line,3b and 3d on HT-29 cell line,and 3b-3d and 3f-3h on K562 cell line has remarkably and significantly enhanced than that of quercetin,and the present research results provide a suggestive preliminary SAR.

关 键 词：槲皮素衍生物 设计合成 构效关系 抗肿瘤 

分 类 号：R931.6[医药卫生—生药学]