基于药效团模型的DHODH抑制剂构效关系研究

CORC > 北京大学 > 化学与分子工程学院

	基于药效团模型的DHODH抑制剂构效关系研究; Structure-activity Relationship Studies on Inhibitors of Dihydroorotate Dehydrogenase Based on Pharmacophore Model
	鲍红娟 ; 唐亚林 ; 徐筱杰 ; 向俊锋 ; 郑智慧 ; 路新华
刊名	高等学校化学学报
	2010
关键词	DHODH抑制剂构效关系药效团模型虚拟筛选 Dihydroorotate dehydrogenase inhibitor Structure-activity relationship Pharmacophore model Virtual screening
英文摘要	利用药效团模型研究二氢乳清酸脱氢酶(Dihydroorotate dehydrogenase,DHODH)抑制剂的构效关系,为DHODH抑制剂的虚拟筛选提供新的方法.以31个具有DHODH抑制活性的化合物为训练集化合物,半数抑制浓度(IC50)范围为7~63000 nmol/L,利用Catalyst/HypoGen算法构建DHODH抑制剂药效团模型,通过对训练集化合物多个构象进行叠合,提取药效团特征及三维空间限制构建药效团模型.利用基于CatScramble的交叉验证方法及评价模型对已知活性化合物的活性预测能力,确定较优药效团模型.模型包含1个氢键受体、3个疏水中心,表征了受体配体相互作用时可...; The pharmacophore model of dihydroorotate dehydrogenase inhibitors was established guide the investigation on virtual screening for new dihydroorotate dehydrogenase inhibitors. Based on the training set composed of 31 DHODH inhibitors, pharmacophore models were generated by HypoGen program of the Catalyst software. The IC(50) of the inhibitors varied from 7 to 63000 nmol/L. The pharmacophore models were a set of 3D pharmacophore features, which were constructed by the generation of conformational models and alignments of conformations based on the training set. The best model was validated to be highly predictive by two methods, namely, test set prediction and CatScramble method. This model consisted of two hydrogen-bond acceptors, and two hydrophobic regions. These features in the three-dimensional arrangement in the pharmacophore model could be characterized as hydrogen bond interaction, hydrophobic interaction and pi-pi interaction between ligand and acceptor. These features play an important role in determining the activities of bioactive molecules. The model's correlation coefficient between the estimated and true activities for compounds constituting the training set were 0.8405, and for compounds from microbial metabolites were 0.8788. Using the pharmacophore model of DHODH inhibitors, 59 compounds with good estimated activities were found from microbial metabolites. New DHODH inhibitors may be found from these candidate compounds.; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000278159700017&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; SCI(E); 中文核心期刊要目总览(PKU); 中国科技核心期刊(ISTIC); 中国科学引文数据库(CSCD); 3; 05; 938-946; 31
语种	中文
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/244450]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	鲍红娟,唐亚林,徐筱杰,等. 基于药效团模型的DHODH抑制剂构效关系研究, Structure-activity Relationship Studies on Inhibitors of Dihydroorotate Dehydrogenase Based on Pharmacophore Model[J]. 高等学校化学学报,2010.
APA	鲍红娟,唐亚林,徐筱杰,向俊锋,郑智慧,&路新华.(2010).基于药效团模型的DHODH抑制剂构效关系研究.高等学校化学学报.
MLA	鲍红娟,et al."基于药效团模型的DHODH抑制剂构效关系研究".高等学校化学学报 (2010).