基于计算机辅助药物设计的水飞蓟宾结构改造及体外活性研究
Structural Modification and Activity in Vitro Study of Silybin Based on Computer-Aided Drug Design
高诗特 1杨兴博 1胡亚男 1时元元 1郑志航1
作者信息
- 1. 沈阳科技学院,辽宁 沈阳 110166
- 折叠
摘要
目的:利用周期蛋白依赖性激酶 4/6(CDK4/6)抑制剂构建药效团模型,对天然产物水飞蓟宾进行结构改造.方法:采用计算机辅助药物设计技术,分析靶蛋白活性空腔内的关键氨基酸与小分子的结合方式.采用MTT法,在人乳腺癌细胞(MCF-7)和肝癌细胞(HepG-2)中对目标化合物进行了初步的体外抗肿瘤活性研究.结果:合成产物的体外活性均高于水飞蓟宾,化合物I3 与蛋白结合较好,对MCF-7 和HepG-2 的半抑制浓度分别为 29.97 μmol/L和 20.66 μmol/L.结论:水飞蓟宾衍生物的结构改造值得进一步研究.
Abstract
Objective:To construct a pharmacophore model based on the marketed cyclin-dependent kinases 4/6(CDK4/6)inhibitors,and to modify the structure of the C-7 position of silybin in natural products.Methods:Computer-aided drug design technology is used to analyze the binding mode of key amino acids and small molecules in the active cavity of the target protein.Preliminary in vitro anti-tumor activity studies of the target compounds are carried out in human breast cancer cells(MCF-7)and hepatocellular carcinoma cells(HepG-2)using MTT method.Results:The activity of the synthesized products in vitro is higher than that of silybin,and compound I3 is well bound to protein,and the semi-inhibitory concentrations of MCF-7 and HepG-2 are 29.97 μmol/L and 20.66 μmol/L,respectively.Conclusion:The structural modification of silybin derivatives deserves further study.
关键词
水飞蓟宾/合成/活性研究Key words
silybin/compound/activity research引用本文复制引用
出版年
2024
NETL
NSTL
维普
万方数据