3D-QSAR技术在筛选五环三萜皂苷先导化合物中的应用策略

Application strategy of 3D-QSAR in screening pentacyclic triterpenoid saponins

明确的构效关系(SAR)是新药设计和研发的基础;一种先导化合物的成功筛选和发现,是新药研制成功的先决条件。合理应用定量构效关系(QSAR)进行定量药物设计,可以大大缩短研发周期,提高研发效率。研究定量构效关系的途径有多种,其结果的可行度大小,取决于其所采用的结构参数化方法、数学模型及数据的质量。目前,3D-QSAR已经成为了包括中药研发领域在内的最重要前期药物设计手段,其核心是分析方法和定量构效关系模型的建立。五环三萜皂苷作为天然药物中含量最为丰富的三萜皂苷之一,具有广泛的生物活性和药效作用,以其作为先导化合物,具有巨大的研究价值和较高的成药潜力。文章主要从QSAR的概念、发展过程、分析方法出发,结合五环三萜皂苷的分子结构特性和近年的研究实例,总结和归纳了3D-QSAR技术在筛选五环三萜皂苷先导化合物中的应用策略和一般研究步骤,并对QSAR未来发展方向进行了展望。

The explicit structure-activity relationship(SAR)is the basis of new drug design and development;The successful screening and discovery of a lead compound is a prerequisite for the successful development of natural product drugs.Using QSAR for quantitative drug design rational can greatly shorten the development cycle and improve the efficiency of research and development.There are many ways to study the QSAR,however,the feasibility of the results depends on the structural parameterization method,mathematical model and data quality.At present,QSAR has become the most important preliminary drug design method,including the research and development of TCM,and its core is the analysis method and the establishment of quantitative structure-activity relationship model.Pentacyclic triterpenoid saponin(PTS)has a wide range of biological activities and pharmacodynamic effects,takes it as a lead compound,the great research value and high potential of patent medicine is predictable.This article combines the concept,development process and analytical method of QSAR with molecular structure characteristics of PTS and recent examples,summarizes and concludes the application strategy of QSAR in screening PTS and the future development direction of QSAR has been prospected.