Assessing the Efficacy of Various NOX Enzyme Inhibitors as Potential Treatments for Ischemic Stroke in Silico

Ischemic stroke occurs when blood flow to the brain is interrupted, causing brain damage. There is evidence that ROS (reactive oxygen species) are produced by the enzyme family NADPH oxidase (NOX) following ischemic stroke, which leads to further brain injury. The ADMET profiles of each inhibitor was taken, in which four classifications, namely applicability domain, human intestinal absorption, blood brain barrier, and human oral bioavailability, were observed. Then, AutoDock Vina was used to model the docking of the inhibitors: VAS2870, GSK2795039, Apocynin, and AEBSF to NOX2, an isoform of the NOX family. The binding affinities of each of the inhibitors to NOX2 were recorded, and the value was used to calculate the Ki value of each inhibitor. It was found that VAS2870 and Apocynin were the most potent NOX2 inhibitors (p < 0.001). All the inhibitors did inhibit the NOX2 enzymes, and they all had favorable ADMET profiles. This study helps corroborate previous in vivo and in vitro studies in an in silico format, and can be used towards evidence for developing drugs to treat ischemic stroke.