中药当归中靶向于群感机制的抗耐药菌活性物质研究

项目名称： 中药当归中靶向于群感机制的抗耐药菌活性物质研究

项目编号： No.81202889

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 郑俊霞

作者单位： 广东工业大学

项目金额： 23万元

中文摘要： 抗生素耐药性是全球严重的公共卫生问题，亟待解决。群体感应(QS)是细菌产生耐药性的重要机制之一。本课题组通过对临床上抗菌有效方剂组方中药进行分析，找出当归等一批高频出现的中药。基于QS系统的lasR受体及AHL分子对这些中药已报道的两千多种化学成分进行虚拟筛选，并结合提取物的生物膜抑制活性实验结果，确定当归具有较好的QS抑制活性。本项目拟在前期工作基础上，开展有效中药当归QS抑制活性物质研究：系统分离、鉴定当归中的化学成分；运用生物膜抑制活性模型，评价单体化合物活性；使用QSIS筛选体系，研究活性化合物与QS相关基因关系；利用活性单体化合物与lasR受体对接，进一步验证和解释其作用机制；应用3D-QSAR模块，研究化合物构效关系，寻找先导化合物。本项目拟综合应用传统医药学和现代科学，阐明传统中药当归抗耐药菌作用的科学内涵，为解决抗生素耐药性提供一条新途径，具有重要意义和潜在的应用价值。

中文关键词： 耐药菌；当归；活性物质；虚拟筛选；生物膜

英文摘要： Antibiotic resistance is a serious global public health problem. Quorum sensing (QS) system has been a promising target for developing novel approaches to controlling bacterial infections. Angelica sinensis and other traditional Chinese medicines were identified high-frequency in the anti-bacterial prescription used in clinical. The potent QS inhibitory activity of Angelica sinensis was confirmed by the biofilm inhibitory activity of the extractions and virtual screening for 2000 chemical constituents reported in these high-frequency herbs based on the lasR receptor and AHL molecules. On the basis of previous work, the project aims to study the active constituents of Angelica sinensis QS inhibition: separation and identification of the chemical constituents of Angelica sinensis; biofilm inhibitory activity evaluation of the compounds; relationships of the active compounds with QS-related genes by QSIS screening system; further verification and explanation of the molecular mechanisms by docking with the lasR receptor; structural optimization to looking for lead compounds based on 3D-QSAR. Comprehensive application of traditional medicine and modern science, this project intends to clarify the scientific connotation of Angelica sinensis against antibiotic resistant bacteria, provide a new pattern to resolve this

英文关键词： Antibiotic resistant bacteria；Angelica sinensis；active constituents；Virtual Screening；biofilm