| 蒯振彧,朱正飞,曾宣,等.基于计算机模拟的丹参中黄酮类化合物抗肿瘤活性筛选[J].安徽医药,2023,27(6):1098-1102. |
| 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 |
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| DOI：10.3969/j.issn.1009-6469.2023.06.009 |
| 中文关键词: 丹参 计算机，模拟 黄酮类 抗肿瘤 分子对接 ADMET预测 |
| 英文关键词: Salvia miltiorrhiza Computers, analog Flavones Anti-cancer Molecular docking ADMET |
| 基金项目:安徽省高校自然科学研究项目( KJ2021A1340) |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| 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 functionwas used to judge the binding ability of ligand molecules and screen active compounds; according to Lipinski′s five rules, Filter byLipinski module was used to conduct pre-screening and evaluation of drug-like properties and the Discovery Studio software was usedto analyze the ADMET (absorption, distribution, metabolism, excretion, toxicity); In vitro bioactivity validation of best compound wasperformed by Biacore assay and we predicted the binding mode between dihydrotanshinone Ⅰ and ARL2 protein by utilizing moleculardocking.Results The binding function scores of dihydrotanshinone Ⅰ, neocryptotanshinone and tanshinone Ⅵ with tumor target proteins were higher than 7, and showed reasonable drug properties, which refered to high binding ability and good activity, among whichdihydrotanshinone Ⅰ was the best. Molecular docking showed that multiple structures in dihydrotanshinone Ⅰ could hydrogen bondwith amino acid residues (ARG61) of ARL2.Conclusion The dihydrotanshinone Ⅰ in Salvia miltiorrhiza shows strong drug-like properties and has good interaction with ARL2. |
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