酰腙类功能配合物抑制丹参枯萎病菌生长代谢的生物量热学研究

Salvia Miltiorrhiza, the active ingredient in salvia miltiorrhiza dripping pills, has already become one of the national cardiovascular diseases profession leadership brand in China and been exported to European markets successfully. Markedly, Blight and root rot cause serious damage to the growth of Salvia Miltiorrhiza. The project is firstly to synthesize the acylhydrazone compounds bearing different function groups with fine bioactivity, strong coordination preference and various coordination fashions, secondly to prepare the novel functional lanthanide coordination compounds with the acylhydrazone compounds as ligands, which exhibit a good synergistic effect, and the structures of the coordination compounds will be determined by single crystal X-ray diffraction technique. Followed that, the on-line microcalorimety is employed to monitor the inhibiting effect of the coordination compounds on the growth and metabolism of Salvia Miltiorrhiza blight and root rot pathogenic bacterias, the curve of heat flow against time will be available. Finally, the apparent rate constant, k, of the inhibiting growth and the apparent activation energy, Ea, of the inhibiting growth of pathogenic bacterias will be attained from thermokinetic equations. The inhibiting ration, I, and the half inhibiting concentration, IC50, can be calculated for determination of optimized concentration, temperature and acidity. Based on thermodynamic functions of the inhibiting effect of the coordination compounds on the growth of blight and root, we would be direct to a correlation between the structure and the bioactivity of the coordination compounds. The research results would rapidly screen out the efficiency fungicides on blight and root rot, and a correlation between the structure and the bioactivity would provide guidance to the design of the efficiency fungicide and establish the theoretical foundation for development of Salvia Miltiorrhiza Chinese medicinal crop.

以丹参有效成分为主的丹参滴丸现已成为国内心血管市场上的主导品牌之一，并畅销欧美市场。然而枯萎病和根腐病是丹参生长过程中的最大危害。本研究拟先合成具有优良生物活性、强的配位能力和多样配位方式的不同结构官能团的酰腙，再与同样具有生理活性的稀土离子作用，构筑系列可能具有协同作用的新型功能配合物，培养单晶，测定结构；用微量热法实时监测这些功能配合物对丹参枯萎病菌、丹参根腐病菌的生长代谢的抑制作用，获得热动谱图。通过动力学模型方程解析得到抑制生长速率常数k和细菌生长的激活能Ea，计算得到抑制比I、半抑制浓度IC50、确定出最佳用药浓度、温度和酸度；计算得到生长和抑制过程的热力学函数、关联活性评价。该方法不仅能快速筛选出新型丹参病原菌有效抑杀菌药剂，而且可以利用微量热学的结论研究配合物结构与杀菌能力的构效关系，指导配合物杀菌剂结构的设计，为发展丹参中药材种植产业奠定一定的理论基础。

以丹参有效成分为主的丹参滴丸现已成为国内心血管市场上的主导品牌之一，并畅销欧美市场。然而枯萎病和根腐病是丹参生长过程中的最大危害。按照基金的合成路线现已合成了12种酰腙配体，这些配体具有优良生物活性、强的配位能力和多样配位方式的不同结构官能团。接着利用这些配体与同样具有生理活性的稀土离子作用合成了23种新型功能配合物，且已通过IR，XRD，TG对配合物的晶体结构进行了表征。通过传统生物学平皿菌丝生长速率法筛选抑菌性较好的稀土配合物。用微量热法实时监测筛选出的稀土配合物对丹参枯萎病菌、丹参根腐病菌的生长代谢的抑制作用，获得热动谱图。该方法不仅能快速筛选出新型丹参病原菌有效抑杀菌药剂，而且可以获得配合物结构与杀菌能力的构效关系，指导配合物杀菌剂结构的设计，可以为发展丹参中药材种植产业奠定一定的理论基础。此外微量热法也可以成为今后快速、定量抑菌能力评价方法。项目一共发表了学术论文22篇，其中SCI收录18篇，申报专利一项。