Exploring quinoline ring derivatives as potent integrase inhibitors using Ligand-based modeling studies

摘要：

　　Integrase has become an attractive target for the design of anti-HIV inhibitor because it plays a quite important role in the process of HIV-1 virus replication.The quinoline ring derivatives,which have the similar pharmacophore to β-diketoacids,are the kind of integrase inhibitor with highly antiviral activity.A series of quinoline ring derivatives were analyzed by the Comparative Molecular Field Analysis (CoMFA),comparative molecular similarity induces analysis (CoMSIA) and Topomer CoMFA methods.Firstly,we chose 77 compounds from former papers as a dataset,followed by dividing it into the training set and test set randomly.Then,we constructed predictive models of CoMFA,CoMSIA and Topomer CoMFA,respectively.The CoMFA yielded the best cross-validated model with a q2=0.758,non-cross-validated r2=0.988.The CoMSIA model yielded a q2 =0.701 and r2 =0.986 while the Topomer CoMFA model has q2 =0.661 and r2 = 0.966.Through verification,these results suggested a strong predictive ability to the design of novel highly active HIV-1 integrase inhibitors for therapy.

关键词： Computer-aided drug design 3D-QSAR HIV-1 integrase inhibitor CoMFA CoMSIA Topomer CoMFA

作者: Xiao Hui Sun Jian Qing Guan Jian Jun Tan Chang Liu Cun Xin Wang

作者单位: College of Life Science and Bio-engineering, Beijing University of Technology, Beijing 100124, China

会议类型: 国际会议

会议名称: World Congress on Medical Physics and Biomedical Engineering (2012年医学物理及生物医学工程国际会议(IFMBE))

会议地点: 北京

会议语种:英文

页码: 1276-1279

在线出版日期: 2012-05-26（万方平台首次上网日期，不代表论文的发表时间）