3D-QSAR studies of thiazolidenebenzenesulfonamide derivatives based on Topomer CoMFA method and molecular design

The three-dimensional quantitative structures-activity relationship (3D-QSAR) models were developed from a data set of 21 thiazolidenebenzenesulfonamide derivatives by using Topomer comparative molecular field analysis (Topomer CoMFA) method. The best Topomer CoMFA model had a cross-validation q² value of 0.964, a non cross-validation r² value of 0.801 and an external validation statistic Q_ext² value of 0.959. The study also used the methodology of fragment-based drug design (FBDD) to virtual screen new molecules by using Topomer Search technology. The obtained 3 Ra groups and 7 Rb groups with the highest contribution values were searched from ZINC database, and 21 new molecules with effective high activities were designed. It is demonstrated that Topomer CoMFA model had good stability and predictive ability. Topomer Search technology could be effectively used to screen and design new compound, which provided the basis for the design of new anti-AIDS drugs. (authors)