L-型钙离子通道抑制剂药效团模型的构建

Pharmacophore model construction of L-type calcium channel antagonists

目的构建L-型钙离子通道抑制剂的药效团模型,为从中药化学成分中发现具有钙离子通道抑制作用的成分提供了新的方法,同时为先导物改造成为活性较好的钙离子通道抑制剂提供思路。方法以来源于NCBI数据库中对新西兰兔心脏L-型钙离子通道具有抑制作用的12个化合物为研究对象,利用HipHop定性药效团模型构建方法,建立L-型钙离子通道拮抗剂的药效团模型,利用数据库搜索方法对药效团模型进行优劣评价。结果获得最优药效团模型具有以下几个特征:2个氢键受体和4个疏水基团,其综合评价指数CAI为2.78。结论构建的定性药效团具有一定的可靠性,可用于开展活性化合物筛选和指导先导化合物的结构改造,有助于指导发现中药中的L-型钙离子通道阻滞剂。

Objective This study was amid to construct a pharmacophore model of L-type calcium channel antagonists in the application of a approach for discovering novel L-type calcium channel antagonists from leading compounds by screening traditional Chinese medicine（TCM）database.Methods Qualitative hypotheses were generated by HipHop separately on the basis of 12 compounds with antagonistic action on L-type calcium channel expressed in rabbit cardiac muscle.Database searching method was used to evaluate the hypotheses.Results The results showed that optimal qualitative hypothesis is with certain features,i.e.two hydrogen-bond acceptors,four hydrophobic groups,and the CAI value of 2.78.Conclusion It was concluded that the pharmacophores are reliable and can be used to screen database for novel L-type calcium channel antagonists.