白杨素衍生物的合成及抗肿瘤活性预测  

Synthesis of chrysin derivatives and prediction of anti-tumor activity

作　　者：刘子源 刘永杰 向慧龙 赵静国[1] 徐凌云[1] LIU Zi-yuan;LIU Yong-jie;XIANG Hui-long;ZHAO Jing-guo;XU Ling-yun(Shool of Life Science and Technology,Wuhan Polytechnic University,Wuhan 430023,China)

机构地区：[1]武汉轻工大学生命科学与技术学院,武汉430023

出　　处：《武汉轻工大学学报》2021年第4期35-39,65,共6页Journal of Wuhan Polytechnic University

摘　　要：目的:白杨素具有抗肿瘤等多种药理作用,但是C-5或C-7位羟基易糖基化而降低其生物活性。合成一类7位取代伯酰胺的白杨素衍生物,并对其抗肿瘤活性进行预测。以白杨素为原料,通过亲核取代、水解、氯化和氨解的反应,在白杨素7号位引入了长链伯酰胺,得到两种未见报道的白杨素衍生物,并用1H NMR和13C NMR表征所得化合物的结构;采用MTT法评价白杨素衍生物对卵巢癌细胞株SKOV3的抗肿瘤活性;采用分子对接技术预测化合物与EGFR和VEGFR2的结合活性。结果显示在7位引入长链伯酰胺基团合成得到7-O-乙酰胺(丁酰胺)白杨素具有良好的体外抗肿瘤活性,与EGFR和VEGFR2具有较高的亲和力。7-O-乙酰胺(丁酰胺)白杨素有望开发成抗肿瘤新药。Objective:Chrysin had anti-tumor and many other pharmacological effects,but the C-5 or C-7 hydroxyl group was easily glycosylated and reduced its biological activity.In this paper,a class of chrysin derivatives with primary amides substituted at the 7-position were synthesized and their anti-tumor activities were predicted.Methods:Using chrysin as a raw material,through nucleophilic substitution,hydrolysis,chlorination and ammonolysis,a long-chain primary amide was introduced at position 7 of chrysin,and two unreported chrysin derivatives were obtained.1H NMR and 13C NMR were used to characterize the structure of the obtained compounds.MTT method was used to evaluate the in vitro anti-tumor activity of chrysin derivatives on ovarian cancer cell lines SKOV3.Molecular docking technology was used to predict the binding activity of the compounds with EGFR and VEGFR2.Results:The 7-O-acetamide(butyramide)chrysin was synthesized by introducing a long-chain primary amide group at position 7.It has good anti-tumor activity in vitro and has a high affinity with EGFR and VEGFR2.Conclusion:7-O-acetamide(butyramide)chrysin was expected to be developed as a new anti-tumor drug.

关 键 词：白杨素 衍生物 伯酰胺 抗肿瘤 SKOV3 分子对接 

分 类 号：R969.1[医药卫生—药理学] R285.6[医药卫生—药学]