扎那米韦类衍生物的分子对接、3D-QSAR和分子设计研究  

Molecular Docking, 3D-QSAR and Molecular DesignStudies on Zanamivir Derivatives

作　　者：施建成 赵丹 SHI Jiancheng;ZHAO Dan(School of Chemistry and Materials,Nanning Normal University,Nanning 530001,Guangxi;Key Laboratory of Macromolecular Chemistry and Physics,Nanning Normal University,Nanning 530001,Guangxi)

机构地区：[1]南宁师范大学化学与材料学院,广西南宁530001 [2]南宁师范大学广西天然高分子化学与物理重点实验室,广西南宁530001

出　　处：《四川师范大学学报(自然科学版)》2025年第3期367-374,共8页Journal of Sichuan Normal University(Natural Science)

基　　金：广西自然科学基金(2013GXNSFAA019019)。

摘　　要：探讨扎那米韦类衍生物对禽流感病毒神经氨酸酶(NA)的抑制作用,为新的NA抑制剂的研发和设计提供有用的结构信息,进而对流感病毒的新药研发产生一定的积极意义.首先,选取22个扎那米韦类的合成化合物为配体,与PDB(protein data bank)数据库中下载的3BEQ受体蛋白进行对接.然后,采用CoMFA和CoMSIA方法建立3D-QSAR预测模型,其中,CoMFA和CoMSIA模型的交叉验证系数q^(2)分别为0.599和0.592,非交互验证相关系数R^(2)分别为0.999和0.775,这一结果表明2种模型都具有良好的预测能力.最后,根据对接结果和3D-QSAR模型的预测分析,设计得到2种对禽流感病毒抑制活性更高的分子.To study the inhibitory activity of zanamivir derivatives on the virus neuraminidase of the avian influenza, 22 zanamivir derivatives were selected as ligands and docked with the 3BEQ receptor protein that was downloaded from the PDB(Protein Data Bank)database. The 3D-QSAR model was established by CoMFA and CoMSIA methods, where the cross validation coefficient q^(2) was 0.599 and non-cross validation coefficient R^(2) was 0.999 for CoMFA model, while the cross validation coefficient q^(2) was 0.592 and non-cross validation coefficient R^(2) was 0.775 for CoMSIA model. The results reveal that both models have good predictive capability. Based on the docking results and 3D-QSAR models, the novel melecules with stronger inhibitory activity were designed. The results are expected to provide useful structural information for the development of new neuraminidase inhibitors and have positive significance for the development of new drugs for influenza virus.

关 键 词：扎那米韦衍生物 神经氨酸酶抑制剂 分子对接 3D-QSAR 分子设计 

分 类 号：O62[理学—有机化学]