论文部分内容阅读
目的:利用计算机辅助新药设计(Computer Aided Drug Design,CADD)技术中的受体图像法,对不同类型降血脂药物的化学结构及甘草次酸类的降血脂药效结构进行模型化研究,并初步探讨甘草次酸类的降血脂药理作用机制。方法:利用计算机程序EMO(分子力学程序)和GEOMOS(量子力学)以及Semi-empirical PM3方法,对4种不同类型的32个具有降血脂活性的分子进行分析。通过分子能量的降低和空间结构的优化处理,测定和计算这些分子的有关几何性、电性和能量参数。然后对优化后分子进行类型内重叠和有关参数的类型间对比观察,预测各类分子的共同药效结构和功能基刚。分了重叠的可行性用参数RMS(Root Meam Square)进行判断。结果:分别获得32个降血脂活性分子的4种不同特征的药效基本结构图像,并发现甘草酸类(如18β-甘草次酸)与苯氧乙酸类(fibrates)分子的优化空间构型中,存在类似的特定结构片段,相应原子和原子团的电荷密度分布(netchrges)、3个电荷中心分布及其相间距离具有可观的相似性。说明在甘草酸类的优化空间结构上可能具有与笨氧乙酸类药物类似的药效结构片段存在,甘草次酸及18-脱氢甘草次酸的铵盐降低71％的甘油三酯和51％胆固醇浓度。结论:甘草次酸类可能具有与苯氧乙酸类类似的降血脂作用机理,同时与苯氧乙酸类
OBJECTIVE: To study the chemical structure of different types of antihyperlipidemic drugs and the hypolipidemic pharmacodynamic structures of glycyrrhetinic acid using the receptor image method in Computer Aided Drug Design (CADD) Glycyrrhetinic acid hypoglycemic pharmacological mechanism of action. METHODS: Four different types of 32 hypolipidemic molecules were analyzed using the computer program EMO (Molecular Mechanics Program) and GEOMOS (Quantum Mechanics) and the Semi-empirical PM3 method. Through the reduction of molecular energy and the optimization of the spatial structure, the relevant geometrical, electrical and energy parameters of these molecules are determined and calculated. Then, the optimized molecules are overlapped within the types and the types of related parameters are compared, and the common structure and function of various molecules are predicted. The feasibility of the sub-overlap is judged by the parameter Root (Meam Square). Results: The basic structural images of four different characteristics of 32 hypolipidemic active molecules were obtained respectively. It was found that in the optimized spatial configuration of glycyrrhizinic acid (such as 18β-glycyrrhetinic acid) and fibrates , There is a similar fragment of specific structure with considerable similarity between the netchrges of the corresponding atoms and radicals, the distribution of the three charge centers and their interphase distances. It is indicated that the glycyrrhizic acid may have the similar pharmacophenotypic structure in the optimized spatial structure of glycyrrhizin. The glycyrrhetinic acid and the ammonium salt of 18-dehydroagric acid reduce triglyceride by 71% and 51% Cholesterol concentration. CONCLUSION: Glycyrrhetinic acid may have similar hypolipidemic mechanism as phenoxyacetic acid, and at the same time with phenoxyacetic acid