吲哚类CB2配体共同特征药效团的研究及其应用  

Study on the common characteristic pharmacophore of indole CB2 ligands and its application

作　　者：秦政 沈家成 李正夫 周祖浩 王晓斌 李姣姣[1] QIN Zheng;SHEN Jia-cheng;LI Zheng-fu;ZHOU Zu-hao;WANG Xiao-bin;LI Jiao-jiao(College of Pharmacy,Jiangsu Ocean University,Lianyungang 222000,China;College of Computer Engineering,Jiangsu Ocean University,Lianyungang 222000,China;Key Laboratory of Green Pesticide and Agricultural Bioengineering,Ministry of Education,Guiyang 550025,China)

机构地区：[1]江苏海洋大学药学院,江苏连云港222005 [2]江苏海洋大学计算机工程学院,江苏连云港222005 [3]贵州大学绿色农药与农业生物工程教育部重点实验室,贵州贵阳550025

出　　处：《化学研究与应用》2023年第5期1059-1068,共10页Chemical Research and Application

基　　金：江苏省海洋资源开发研究院开放基金课题项目(JSIMR202102)资助;江苏海洋大学研究生科研与实践创新计划项目(KYCX2022-80)资助;江苏海洋大学大学生创新训练项目(SY202211641640010)资助。

摘　　要：CB2与神经退行性疾病、癌症等多种疾病紧密相关,是极具潜力的药物靶点。本文从已报道文献中选取8个具有高亲和力的吲哚类CB2配体为研究对象,采用共同特征药效团(HipHop)方法构建出10个CB2配体药效团模型,并通过测试集验证和ROC曲线验证两种方法对其进行筛选和验证,得到1个最佳药效团模型。最佳药效团模型含有1个芳环中心,3个疏水基团,1个氢键受体特征。随后采用逐级筛选策略,通过该模型对ZINC数据库进行筛选、分子对接、ADMET预测及配体蛋白相互作用分析,最终获得5个对CB2具有潜在活性的化合物,为筛选具有CB2活性的化合物提供理论基础。CB2 receptors are closely related to neurodegenerative diseases,cancer and other diseases,and are potential drug targets.In this paper,8 indole CB2 ligands with high affinity were selected from the reported literature as the research objects,and 10 CB2 ligand pharmacophore models were constructed by the common characteristic pharmacophore(HipHop)method,which was verified by the test set.It was screened and verified by two methods,ROC curve verification,and an optimal pharmacophore model was obtained.The optimal pharmacophore model contains 1 aromatic ring center,3 hydrophobic groups,and 1 hydrogen bond acceptor feature.Then,a step-by-step screening strategy was adopted to conduct virtual screening of the ZINC database through the optimal pharmacophore model,molecular docking,ADMET prediction and ligand-protein interaction analysis,and finally 5 compounds with potential activity on CB2 were obtained.These active compounds provided a theoretical basis.

关 键 词：CB2配体 共同特征 药效团 逐级筛选 

分 类 号：O641.4[理学—物理化学]