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 ...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 toβ-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(Co MFA), comparative molecular similarity induces analysis(Co MSIA) and Topomer Co MFA 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 Co MFA, Co MSIA and Topomer Co MFA, respectively. The Co MFA yielded the best cross-validated model with a q2=0.758, non-cross-validated r2=0.988.The Co MSIA model yielded a q2=0.701 and r2=0.986 while the Topomer Co MFA 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.展开更多
文摘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 toβ-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(Co MFA), comparative molecular similarity induces analysis(Co MSIA) and Topomer Co MFA 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 Co MFA, Co MSIA and Topomer Co MFA, respectively. The Co MFA yielded the best cross-validated model with a q2=0.758, non-cross-validated r2=0.988.The Co MSIA model yielded a q2=0.701 and r2=0.986 while the Topomer Co MFA 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.
