Designing of Promising VEGFR‐2 Inhibitors by Using QSAR Modeling, Molecular Docking, and Molecular Dynamic Simulation: Implications Toward the Treatment of Cancer

Background The vascular endothelial growth factor receptor 2 (VEGFR‐2) is considered one of the most studied therapeutic targets for the treatment of various cancers. Among many heterocyclic compounds, the oxadiazole derivatives have been reported to exhibit significant anticancer activities. Therefore, exploring these derivatives against VEGFR‐2 could provide valuable drug molecules that can be safely utilized for cancer treatment. Method In this study, a wide range of computational techniques, including quantitative structure–activity relationship (QSAR) modeling, molecular docking, and molecular dynamics simulation studies, were used for the systematic development and investigation of oxadiazole derivatives. Twenty‐one new oxadiazole derivatives were synthesized based on a QSAR modeling technique applied to 50 reported oxadiazole compounds with a wide range of anticancer activities. Seven parent compounds, that is, S39 to S45 , along with their newly prepared derivatives, were subjected to the developed QSAR model for the prediction of their IC 50 values. All the new derivatives were then redocked using AutoDock Vina software to validate the QSAR results. Results Of the 21 new derivatives, S43b, S44b, and S45b exhibited significantly improved activity compared to the parent compounds. The results were further validated through molecular dynamics simulation studies. Conclusion All the results of this study provide a guiding pathway for the design and development of new oxadiazole moieties with better anticancer activity.