聚腺苷二磷酸核糖聚合酶-1抑制剂药效团模型的建立  

Construction of pharmacophore model of PARP-1 inhibitor

作　　者：张文婷[1] 鄢浩[2] 姜凤超[1] 

机构地区：[1]华中科技大学同济医学院药学院,湖北武汉430030 [2]华中科技大学同济医学院附属同济医院药学部,湖北武汉430030

出　　处：《药学学报》2007年第3期279-285,共7页Acta Pharmaceutica Sinica

摘　　要：建立聚腺苷二磷酸核糖聚合酶-1[poly(ADP-ribose)polymerase-1,PARP-1]抑制剂的药效团模型,探讨其与PARP-1的作用机制。利用Catalyst软件系统,选择具有较高体外抑制活性的8种结构类型的38个化合物作为训练集,经构象分析,分子叠合等过程构建出药效团模型。结合PARP-1的作用机制等因素,得到一个含有两个氢键接受体和两个芳香疏水性基团的PARP-1抑制剂药效团模型。本文建立的药效团模型的可靠性较高(RMS=0.46,Correl=0.91,Weight=2.06,Config=15.97),不但给出了作用位点的相关信息,而且具有良好的活性预测能力,有助于新型结构的PARP-1抑制剂的设计。To construct the pharmacophore model of the poly （ADP-ribose） polymerase-1 inhibitor and to investigate the possible inhibitory mechanisms, ten pharmacophore models of PARP-1 inhibitor were established from the training set of thirty-eight PARP-1 inhibitors with conformer analysis and pharmacophore mapping by using the Catalyst software. Based on the mechanism of action and the known structure-activity relationship of PARP-1 inhibitor, an optimal pharmacophore model including two hydrogen-bonding acceptors and two aromatic hydrophobic core was confirmed. The reliability of the optimal pharmacophore model is preferably with RMS = 0.46, Correl = 0.91, Weight = 2.06, and Config = 15.97. This pharmacophore model not only provided some information about the interaction between enzyme and compound, but also showed excellent forecast ability and contributes to design the PARP-1 inhibitors with undiscovered structure.

关 键 词：计算机辅助药物设计 PARP-1抑制剂 药效团模型 

分 类 号：R916[医药卫生—药学]