以天然产物活性分子为模板，借助计算机辅助药物设计方法创制无公害渔药是解决水产养殖病害控制、保障食品与环境安全的重要途径之一。本项目在前期研究基础上，以鱼类多子小瓜虫为研究对象，通过对高抗虫活性天然产物—厚朴酚进行取代、Suzuki偶联、克莱森重排等化学反应合成其衍生物及类似物，并测定抗虫活性（EC50）和对鱼类的毒性（LC50）；基于化合物的结构参数和活性数据分别构建定量构效关系（QSAR）模型和药效团模型，阐明化学结构与活性之间的量变规律，确定抗虫和对鱼致毒关键基团的种类、数量及空间排列形式；以此为主要原则设计、合成高效低毒的新型抗小瓜虫活性分子。该项目的研究不仅对研发抗小瓜虫新药及其药理研究提供理论基础和依据，也为其它水产新药的研发提供借鉴和参考，具有重要的科学意义和应用前景。

Taking pharmacology activity molecules from natural products as templates, the discovery of green fishery drugs with computer aided drug design protocols is one of significant ways to control diseases in aquaculture and guarantee the safety of food and environment. The parasitic protozoan Ichthyophthirius multifiliis (Ich), probably accounting for more damage to freshwater fish populations worldwide than any other eukaryote pathogen, is used as the research object of this project. Based on the results of previous studies, this project will use magnolol with high anti-Ich activity as a lead compound, and then synthesize magnolol derivatives and analogues by various organic chemistry reactions, such as substitution reaction, Suzuki coupled reaction, Claisen rearrangement. After the evaluation of anti-Ich activity (EC50) and acute toxicity against fish (LC50), QSAR and pharmacophore model will be respectively built using chemical structural parameters and bioactivity data in order to clarify the law of quantitative change between chemical structures and bioactivities and identify type, amount and arrangement of the key chemical groups for anti-ich and toxic activity against fish. Some molecules with higher efficiency and lower toxicity will be designed and synthesized based on the above rules. This study can offer theoretical basis for development and pharmacological research of new drugs against I. multifiliis, and also provide references for development of other fishery anti-parasite drugs. This project has the significance of theory and application.