博落回植物源杀虫剂的设计、合成与作用机理研究

Right now, biomimetic synthesis of active compounds from plants by chemical methods is the major way to develop botanical insecticide. Benzo[c]phenanthridine alkaloids are the mainly active components of Chinese traditional mosquito repellent herbal Macleaya cordata (Willd) R. Br.. In the present research, we found that these alkaloids have prominent insecticidal activity. However, they are low in plant, composition complex, difficult to extract. In addition, the efficacy is not highly enough and duration short. In this project, we intend to design and synthesis six series compounds by applying such approaches as analogue synthesis, sub-structure coordination and bioisosterism principle, to discover new botanical insecticides with high activity and simple structure. At the same time, using electrophysiological techniques systematically study the effects on the Pieris rapae nervous by the title compounds. Furthermore, fluorescence calcium measurement technique was used to study the modulation on the calcium channel between the plasma membrane and endoplasmic reticulum calcium stores. Through this project, provide useful information for the development of new type botanical insecticide with higher activity, lower toxicity, broader spectrum and clear interaction mechanism.

以植物中杀虫活性化合物为先导，用化学的方法进行仿生合成，是当前开发植物源杀虫剂的主要途径。博落回为我国传统杀虫驱蚊中草药，主要活性成分为苯并菲啶生物碱。基础研究发现，该类生物碱杀虫活性突出，具有开发潜力。但在植物中含量低、成份复杂，提取困难；结构复杂难以合成；药效不够高，持续作用时间短。因此，本项目拟采用前体农药、亚结构拼接和生物电子等排等分子设计思路，并借助计算机辅助进行分子设计，对苯并菲啶生物碱进行仿生合成，以期得到结构简单、高活性的新型植物源杀虫剂。同时，采用电生理实验技术研究目标化合物对菜青虫神经系统的影响；结合荧光测钙技术，探讨其对神经元钙离子通道的调控，从组织上到细胞上深入研究目标化合物的作用机理，为高效、低毒、广谱、作用机理明确的新型植物源杀虫剂的开发奠定基础。

以植物中杀虫活性化合物为先导，用化学的方法进行仿生合成，是当前开发植物源农药的主要途径。本项目采用前体农药、亚结构拼接和生物电子等排等分子设计思路，并借助计算机辅助进行分子设计，对苯并菲啶生物碱进行仿生合成，设计共合成了6个系列117个目标分子。采用浸叶法和速率生长法评价目标化合物杀虫和抑菌活性；同时利用电生理实验技术和荧光测钙技术探寻杀虫作用机理。构效关系研究显示，季铵盐型异喹啉衍生物具有杀虫和抑菌二元生物活性，其季铵盐片段是关键的药效团。初步作用机制表明目标化合物能激活细胞膜上的电压门控钙离子通道，从而致使害虫死亡。再者，目标化合物对多种植物病菌的抑菌活性都优于血根碱，和百菌清相当，具有进一步研究的潜力。本项目的实施为高效、低毒、广谱、作用机理明确的新型植物源杀虫剂的开发奠定基础。