基于虚拟筛选从中药中发现抗铜绿假单胞菌的活性成分  

Discovery of active ingredients against Pseudomonas aeruginosa from traditional Chinese medicine based on Virtual screening

作　　者：徐明鑫 陈双扣[1,2] 管天冰[1,2] 任风鸣 滕金凤[1,2] 谭小庆 XU Ming-xin;CHEN Shuang-kou;GUAN Tian-bing;REN Feng-ming;TENG Jin-feng;TAN Xiao-qing(Chongqing Key Laboratory of Industrial Fermentation Microorganism(Chongqing University of Science and Technology),Chongqing 401331,China;Department of chemistry and chemical engineering,Chongqing University of Science and Technology,Chongqing 401331,China;Institute of Medicinal Plant Cultivation,Chongqing 408435,China)

机构地区：[1]工业发酵微生物重庆市重点实验室(重庆科技学院),重庆401331 [2]重庆科技学院化学化工学院,重庆401331 [3]重庆市药物种植研究所,重庆408435

出　　处：《化学研究与应用》2022年第4期754-763,共10页Chemical Research and Application

基　　金：工业发酵微生物重庆市重点实验室开放基金项目(GYFJWSW-08)资助。

摘　　要：针对铜绿假单胞菌的耐药性问题,采用虚拟筛选技术快速筛选出具有抗铜绿假单胞菌活性的中药成分。采用AutoDock Vina程序对铜绿假单胞菌LasR信号受体蛋白的2UV0、3IX3和6MVM三个共晶结构进行方法学研究,然后利用Lipinsky规则对陶术中药数据库进行初步筛选,通过分子对接进行再次筛选,并对满足Lipinsky规则且结合能低于阈值的化合物开展体外抑菌实验。研究结果表明3IX3靶点蛋白分子对接模型具有较强的活性分子富集能力,基于该模型对陶术中药数据库进行虚拟筛选后发现符合Lipinsky规则且结合能低于阈值的化合物7个,目筛后得到潜在活性分子5个,体外抑菌实验发现黄芩素-7-甲醚有明显抗菌活性,其最小抑菌浓度为500μg·mL^(-1)。本研究理论结合实验发现黄芩素-7-甲醚有较好的抗铜绿假单胞菌活性,对抗菌新药的研发具有一定的参考价值。In order to solve the problem of drug resistance of Pseudomonas aeruginosa,virtual screening technology was used to quickly screen out the traditional Chinese medicine ingredients with anti-pseudomonas aeruginosa activity.Methodological research was performed to study the eutectic structures of 2 UV0,3 IX3 and 6 MVM of LasR signal receptor proteins in Pseudomonas aeruginosa through the AutoDock Vina program.Topscience Chinese medicine database was preliminarily screened by Lipinsky rule,and screened again through molecular docking technology.In addition,in vitro antibacterial experiments were carried out on ingredients that met Lipinsky’s rule and had binding energy lower than threshold value.The results showed that the molecular docking model of the 3 IX3 target protein had the stronger enrichment ability for active molecules.7 ingredients of Topscience Chinese medicine database complied with Lipinsky’s rule and had binding energy lower than threshold value were discovered based on the molecular docking model of the 3 IX3 target protein.In vitro antibacterial experiments found that baicalein-7-methyl ether had obvious antibacterial activity,and the minimum inhibitory concentration was 500μg·mL^(-1).In this study,the theoretical calculation method combined with the experimental results showed that baicalein-7-methyl ether had a good anti-Pseudomonas aeruginosa activity,which would be helpful to the development of new antibacterial drugs.

关 键 词：铜绿假单胞菌 分子对接 虚拟筛选 中药成分 

分 类 号：R284[医药卫生—中药学]