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 beta 5 and beta 6 subunit of the 20S proteasome. The constructed CoMFA and CoMSIA models produced statistically significant results with the cross-validated correlation coefficients q(2) of 0.831 and 0.851, non-cross-validated correlation coefficients r(2) of 0.974 and 0.965, and predicted correction coefficients r(pred)(2) 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.