基于血吸虫防治活性的小分子荧光探针的设计与合成及其应用

项目名称： 基于血吸虫防治活性的小分子荧光探针的设计与合成及其应用

项目编号： No.21302022

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 钱益平

作者单位： 赣南师范学院

项目金额： 25万元

中文摘要： 目前，血吸虫病仍然是严重影响我国人民身体健康的重大传染病之一。吡喹酮作为惟一的抗血吸虫药物，迄今其确切作用机制尚未被阐明，而且基本对血吸虫童虫无效。随着吡喹酮被广泛持久和反复使用，其耐药性和反复感染等问题已引起人们的担忧。因此，本项目的目的是基于血吸虫防治活性药物分子设计合成荧光探针，阐明药物作用机制，筛选新型血吸虫防治药物。包括3方面研究：1.设计合成高特异性低毒的血吸虫防治药物荧光探针；2.利用荧光探针技术研究血吸虫防治药物的确切作用方式和作用机制；3.设计合成血吸虫防治药物NO供体-吡喹酮分子，评价其抗血吸虫活性，利用荧光探针技术探讨其作用机制。通过这些研究阐明血吸虫防治药物的作用机制，筛选出1-2个具有抗血吸虫成虫和童虫作用的NO供体-吡喹酮候选药物。

中文关键词： 血吸虫；合成；荧光探针；NO 供体-吡喹酮；机理

英文摘要： Schistosomiasis is one of the major parasitic disease and remains a serious public health problem in China today. Praziquantel as the only drug to schistosomiasis, its mechanism of action remains unknown, and which is poor effective against the immature worms，and its increasingly widespread use fuels concerns about drug resistance developing. Therefore, the aims of this project is based on the antischistosomal activity of drug design and synthesis fluorescent probes and study on their mechanisms，and further screening antischistosomal new drugs screening. First, design and synthesis high specificity and low toxicity fluorescent probes of antischistosomal drugs. Second, research the mechanisms and the distributions of antischistosomal drugs by fluorescent probe technology. Third, design and synthesis of NO donor-praziquantel moleculars and their fluorescent probes, assess their activities and study their role of mechanisms by fluorescent probe technology. We hope through these studies to identify new mechanisms of action of schistosomiasis drug, and find one to two NO donor-praziquantel candidates drug against against both immature and adult schistosomiasis.

英文关键词： Schistosomiasis；Synthesis；Fluorescencent probe；NO donor-praziquantel；Mechanism