苯基咪唑类Pin1抑制剂的2D-QSAR研究  

2D-QSAR Studies on Phenyl Imidazoles as Inhibitors of Pin1

作　　者：宋新焕 谢惠定[1] 陈丽君[1] 邱开雄[1] 

机构地区：[1]昆明医科大学药学院暨云南省天然药物药理重点实验室,云南昆明650500

出　　处：《昆明医科大学学报》2015年第8期23-27,共5页Journal of Kunming Medical University

基　　金：云南省教育厅科学研究基金资助项目(2014J044)

摘　　要：目的为苯基咪唑类化合物建立一个有效的2D-QSAR模型来预测其抑制Pin1的活性,对其抑制Pin1机理研究和发现高活性的苯基咪唑类化合物提供参考和帮助.方法采用密度泛函理论、分子力学、和统计学相组合的方法,对21个具有抑制Pin1的苯基咪唑类化合物进行了二维的定量构效关系(2D-QSAR)的研究.结果所建立的2D-QSAR模型方程的复相关系数较大(R达到0.667),具有良好的似合度.结论苯基咪唑类化合物分子的最低未占据空轨道能越小和化合物R2基团的表面积(SR2)越大对Pin1的抑制活性越有利.Objective To establish an efficient 2D- QSAR model for Phenyl imidazoles to predict their inhibitory activities on Pin1 and expect that the theoretical results can offer some useful references for understanding the inhibition mechanism and directing the design and more potential anti- pin1. Methods The Two- dimensional Quantitative structure- activity Relationship（2D- QSAR） of 21 Phenyl imidazoles, which exhibited inhibitory activities of Pin1, was studied with a combined method of density functional theory（DFT）,molecular mechanics（MM＋） and statistics. Result The established 2D- QSAR model showed a reasonable regressive performance（R=0.667）. Conclusion The lower the lowest unoccupied molecular orbital energy and the larger the surface aree R2group（SR2） of phenyl imidazole compounds, the higher the inhibitory activities of Pin1.

关 键 词：二维定量构效关系 苯基咪唑类化合物 肽基脯酰胺顺反异构酶 

分 类 号：R914[医药卫生—药物化学]