喹唑啉类端锚聚合酶抑制剂3D-QSAR和分子对接研究  

Docking and 3D-QSAR Studies on Quinazoline Derivative as TNKS Inhibitors

作　　者：陈小中 沈燕 王娟 胡勇 林治华 CHEN Xiaozhong;SHEN Yan;WANG Juan;HU Yong;LIN Zhihua(Department of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China)

机构地区：[1]重庆理工大学药学与生物工程学院,重庆400054

出　　处：《重庆理工大学学报（自然科学）》2022年第2期224-231,共8页Journal of Chongqing University of Technology：Natural Science

基　　金：国家自然科学基金项目(81171508);重庆理工大学启动基金项目;重庆理工大学研究生创新项目(clgycx20203177)。

摘　　要：利用分子力场分析法(comparative molecular field analysis,CoMFA)、比较分子相似性指数法(comparative molecular similarity indices analysis,CoMSIA)和分子对接方法对一系列喹唑啉类TNKS抑制剂进行三维定量构效关系研究。构建的CoMFA(q^(2)=0.578,r^(2)=0.998,r^(2)_(pred)=0.815)和CoMSIA(q^(2)=0.624,r^(2)=0.929,r^(2)_(pred)=0.747)模型具有良好的鲁棒性、预测能力和机制可解释能力。分子对接实验结果表明:Ser1221和Gly1185是影响这些抑制剂活性的主要氨基酸。研究对设计新型TNKS抑制剂具有参考意义。Thetankyrases(TNKS)is a member of the poly(ADP-ribose)polymerase(PARP)family that have been identified as an potential target for cancer treatment.In this work,a series of quinazoline TNKS inhibitors are subjected to three-dimensional quantitative structure-activity relationship(3D-QSAR)using comparative molecular field analysis(CoMFA),comparative molecular similarity indices analysis(CoMSIA)and molecular docking.The CoMFA(q^(2)=0.578,r^(2)=0.998,r^(2)_(pred)=0.815)and CoMSIA(q^(2)=0.624,r^(2)=0.929,r^(2)_(pred)=0.747)models have good robustness,and predictive ability has good robustness,predictive ability.Molecular docking suggests that the Ser1221 and Gly1185 are the main acids affecting the biological activity of these inhibitors.In future,this study might be useful for design of novel TNKS inhibitors.

关 键 词：分子力场分析法 比较分子相似性指数法 分子对接 TNKS 

分 类 号：R914.2[医药卫生—药物化学]