吲哚类CB2配体3D-QSAR模型的构建与比较  

Construction and Comparison of Indole CB2 Ligand 3D-QSAR Model

作　　者：沈家成 姜筝 孙盛鑫 周祖浩 陈佳吟 李姣姣 SHEN Jiacheng;JIANG Zheng;SUN Shengxin;ZHOU Zuhao;CHEN Jiayin;LI Jiaojiao(College of Pharmacy,Jiangsu Ocean University,Jiangsu Lianyungang 222000;Center for Research and Development of Fine Chemicals of Guizhou University,Guizhou Guiyang 550025,China)

机构地区：[1]江苏海洋大学药学院,江苏连云港222000 [2]贵州大学精细化工研究开发中心,贵州贵阳550025

出　　处：《广州化工》2024年第23期109-113,共5页GuangZhou Chemical Industry

基　　金：江苏海洋大学研究生科研与实践创新计划项目(KYCX2022-80);2022年江苏海洋大学大学生创新训练项目(SY202211641640010);2023年江苏海洋大学大学生创新训练项目(2023-474)。

摘　　要：大麻素2型受体可在多种病理情况下发挥作用,与各种神经退行性疾病、肾小管线粒体功能障碍和肾脏衰竭、抗炎镇痛、免疫调节、溃疡性结肠炎、缺血性卒中、骨质疏松、代谢障碍以及癌症等各类疾病的作用机制息息相关,显示出良好的治疗前景。为研究吲哚类CB2配体的3D-QSAR模型,选取22个吲哚类CB2配体,构建两个不同的训练集,使用3D-QSAR中CoMFA和CoMSIA方法构建四个可靠稳定且具有良好的预测能力的模型。其中3D-QSAR模型的结果为CoMFA 1(q^(2)=0.645,r^(2)=0.984)、CoMSIA 1(q^(2)=0.516,r^(2)=0.970)与CoMFA_(2)(q^(2)=0.619,r^(2)=0.975)、CoMSIA_(2)(q^(2)=0.674,r^(2)=0.974),进一步采用测试集以及Y-随机化试验进行外部验证,结果显示四个模型均满足相应的验证标准,表明模型具有良好的预测能力。并对等势图进行分析,为后续吲哚类CB2配体的设计提供一定的理论参考。Cannabinoid type 2 receptors can play a role in a variety of pathological conditions,and are closely related to the mechanism of action of various neurodegenerative diseases,renal tubular mitochondrial dysfunction and kidney failure,anti-inflammatory analgesia,immune regulation,ulcerative colitis,ischemic stroke,osteoporosis,metabolic disorders,cancer and other diseases,showing a good therapeutic prospect.In order to study 3D-QSAR models of indole CB2 ligands,22 indole CB2 ligands were selected to construct two different training sets,and four reliable and stable models with good predictive ability were constructed using CoMFA and CoMSIA methods in 3D-QSAR.Among them,the results of 3D-QSAR model are CoMFA 1(q^(2)=0.645,r^(2)=0.984),CoMSIA 1(q^(2)=0.516,r^(2)=0.970)and CoMFA_(2)(q^(2)=0.619,r^(2)=0.975),CoMSIA_(2)(q^(2)=0.674,r^(2)=0.974),and the test set and Y-randomized experiment were further used for external verification.The results showed that all four models met the corresponding verification criteria,indicating that the model had good predictive ability.The isopotential diagram was analyzed to provide a theoretical reference for the subsequent design of indole CB2 ligands.

关 键 词：吲哚类CB2配体 3D-QSAR 模型验证 等势图 

分 类 号：O641[理学—物理化学]