基于PTK靶点的黄芪中黄酮化合物抗肿瘤筛选及活性研究  

Anti-tumor screening and activity study of flavonoids in Astragali radix based on PTK target

作　　者：蒯振彧 吴凌燕 曾宣[1] 朱正飞 孟艳秋 KUAI Zhenyu;WU Lingyan;ZENG Xuan;ZHU Zhengfei;MENG Yanqiu(Department of Medical Nursing,Maanshan Technical College,Maanshan 243031,China;Department of Pharmaceutical Engineering,Shenyang University of Chemical Technology,Shenyang 110142,China)

机构地区：[1]马鞍山职业技术学院医学护理系,安徽马鞍山243031 [2]沈阳化工大学制药与生物工程学院,辽宁沈阳110142

出　　处：《沈阳药科大学学报》2025年第2期162-169,共8页Journal of Shenyang Pharmaceutical University

基　　金：安徽省高校自然科学研究项目(2024AH051790,2022AH052970)。

摘　　要：目的运用计算机辅助药物设计对黄芪中黄酮类化合物的抗肿瘤活性进行筛选。方法使用Sybyl软件Surflex-dock模块对小分子与蛋白酪氨酸激酶(protein tyrosine kinases,PTK)进行分子对接,通过Total Score函数分值判断配体分子结合能力,筛选活性化合物,根据Lipinski五法则,使用Swiss ADME预测所研究化合物的药动学特性,最后将筛选出的最优化合物与PTK进行分子动力学模拟及体外分子水平实验,利用分子对接分析化合物与PTK蛋白的相互作用模式。结果筛选出的槲皮素具有最佳的药物样特性并进行分子动力学模拟,利用体外表面等离子共振法验证了化合物与PTK之间具有较高的结合能力,KD值为1.44×10^(-6)μmol·L^(-1)。分子对接显示,槲皮素中多个羟基结构与PTK的氨基酸残基以氢键结合。结论筛选出黄芪中黄酮类化合物槲皮素的抑癌效果很可能通过抑制PTK的激活实现,槲皮素可作为先导化合物进行优化。Objective To screen the anti-tumor activity of flavonoids in Astragali radix with computer-aided drug design.Methods The Surflex-dock module of SYBYL was used for molecular docking that between small molecules and protein tyrosine kinase(PTK),the total score function was used to judge the binding ability of ligand molecules and screen active compounds;according to Lipinski′s five rules,the Swiss ADME was used to analyze the ADMET,finally,the in vitro bioactivity validation of best compound was performed by SPR assay and we predicted the binding mode between quercetin and PTK protein by utilizing molecular docking.Results Quercetin have high binding ability with PTK and strong drug-like properties,SPR assay verified that quercetin could bind PTK,KD value of 1,44×10^(-6)μmol·L^(-1),Molecular docking showed that multiple structures in quercetin could hydrogen bond with amino acid residues of PTK.Conclusion The flavonoid quercetin in Astragali radix was screened to bind to PTK and have inhibitory effect,quercetin could be used as a lead compound for optimization.

关 键 词：黄芪 槲皮素 蛋白酪氨酸激酶 分子对接 先导化合物 

分 类 号：R914[医药卫生—药物化学]