Combined Three Dimensional Quantitative Structure Activity Relationships (3D-QSAR) Modeling and Molecular Docking Studies on Naphthoquinone Analogs as Proteasome Inhibitors

Proteasome inhibitors have been proved to be effective in regulated intracellular proteolysis. Three Dimensional Quantitative Structure Activity Relationships and Molecular docking methods were performed on naphthoquinone analogs as proteasome inhibitors. The bioactive conformation was explored by docking the potent compound 29 into the β5 and β6 subunit of the 20S proteasome. The constructed CoMFA and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients q2 of 0.831 and 0.851, non-cross-validated correlation coefficients r2 of 0.974 and 0.965, and predicted correction coefficients r2 pred of 0.758 and 0.701, respectively. A set of 15 new analogs were proposed by utilizing the results revealed in the present study, and were predicted with significantly improved potencies in the developed models.