基于计算机模拟的丹参中黄酮类化合物抗肿瘤活性筛选  

In silico study of anti-tumor activity of flavonoids in Salvia miltiorrhiza

作　　者：蒯振彧 朱正飞 曾宣[1] 陈泓蓉 KUAI Zhenyu;ZHU Zhengfei;ZENG Xuan;CHEN Hongrong(Department of Pharmacy Teaching and Research,Maanshan technical college,Maanshan,Anhui 243031,China)

机构地区：[1]马鞍山职业技术学院药学教研室,安徽马鞍山243031

出　　处：《安徽医药》2023年第6期1098-1102,共5页Anhui Medical and Pharmaceutical Journal

基　　金：安徽省高校自然科学研究项目(KJ2021A1340)。

摘　　要：目的 运用计算机辅助药物设计对丹参中黄酮的抗肿瘤活性进行虚拟筛选。方法 于2021年12月至2022年3月,使用Sybyl软件的Surflex-dock模块对小分子与靶蛋白进行分子对接,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Discovery Studio 2019 Client的Filter by Lipinski模块进行类药性预筛选评估;并进行ADMET(吸收,分布,代谢,排泄,毒性)预测;将筛选出的最优化合物与靶点蛋白进行Biacore体外结合测试,利用分子对接预测化合物与靶点蛋白的相互作用模式。结果 二氢丹参酮Ⅰ、新隐丹参酮和丹参酮Ⅵ与肿瘤靶点蛋白结合函数分值>7,并表现合理的类药性质,即具有较高的结合能力和良好的类药活性,二氢丹参酮Ⅰ最优。分子对接显示,二氢丹参酮Ⅰ与ADP-核糖基化因子样2受体的氨基酸残基精氨酸61(ARG61)以氢键结合。结论 筛选出丹参中黄酮类化合物二氢丹参酮Ⅰ表现很强的类药性,与ADP-核糖基化因子样2受体结合响应值高。Objective To screen the anti-tumor activity of flavonoids in Salvia miltiorrhiza with computer-aided drug design.Meth⁃ods The Surflex-dock module of SYBYL was used for molecular docking from December 2021 to March 2022,the total score function was used to judge the binding ability of ligand molecules and screen active compounds;according to Lipinski's five rules,Filter by Lipinski module was used to conduct pre-screening and evaluation of drug-like properties and the Discovery Studio software was used to analyze the ADMET(absorption,distribution,metabolism,excretion,toxicity);In vitro bioactivity validation of best compound was performed by Biacore assay and we predicted the binding mode between dihydrotanshinoneⅠand ARL2 protein by utilizing molecular docking.Results The binding function scores of dihydrotanshinoneⅠ,neocryptotanshinone and tanshinoneⅥwith tumor target proteins were higher than 7,and showed reasonable drug properties,which refered to high binding ability and good activity,among which dihydrotanshinoneⅠwas the best.Molecular docking showed that multiple structures in dihydrotanshinoneⅠcould hydrogen bond with amino acid residues(ARG61)of ARL2.Conclusion The dihydrotanshinoneⅠin Salvia miltiorrhiza shows strong drug-like properties and has good interaction with ARL2.

关 键 词：丹参 计算机 模拟 黄酮类 抗肿瘤 分子对接 ADMET预测 

分 类 号：R284.1[医药卫生—中药学]