天然源苯酞类小分子结构优化、抑菌活性及3D-QSAR研究

传统化学农药严重危害人类健康，研发新型无公害绿色农药迫在眉睫。以结构新颖的天然活性物质为先导化合物进行结构的多级优化，是发掘高效、低毒新农药的有效途径。本项目拟在前期研究基础之上，以具有潜在抑菌活性的天然苯酞类化合物Z-3-butylidenephthalide和(Z)-ligustilide为先导化合物，基于合理的药物设计手段，以改善母体化合物理化性质、提高生物活性为目的进行多位点结构修饰，同步进行抑菌活性评价、三维定量构效关系（3D-QSAR）分析及作用机制和成药性研究，为进一步开发基于苯酞骨架的新型植物源杀菌剂提供理论依据和候选化合物。

As human health was seriously jeopardized by the traditional chemical pesticide, the process of discovering novel biorational pesticide was extremely urgent. In recent years, taking plant active substances as lead compounds to proceed multi-level structural optimization has become an effective way to discover new pesticides with high efficiency and low toxicity. Based on the previous research work, this project intends to select the natural phthalides Z-3-butylidenethalide and (Z)-ligustilide as the lead compounds, a series of novel phthalide derivatives will be designed and synthesized based on reasonable drug design methods for the purpose of improving their physicochemical properties and biological activity. In addition, through evaluation of compounds antifungal activity, analysis of three dimensional quantitative structure-activity relationship (3D-QSAR), elucidation of mechanism of action and medicinal properties to provide the theoretical basis and candidate compounds for the further development of new botanical fungicides based on phthalide skeleton.