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

(1) Thomas Jefferson High School for Science & Technology, Alexandria, Virginia

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Ischemic stroke occurs when blood flow to the brain is interrupted, causing brain damage. There is evidence that reactive oxygen species, ROS, are produced by the enzyme family NADPH oxidase (NOX) following ischemic stroke, which leads to further brain injury. This study investigated the effectiveness of different NOX inhibitors as treatments for ischemic stroke in silico. The ADMET (absorption, distribution, metabolism, excretion, and toxicity) profile of each NOX inhibitor was taken, in which four classifications, namely applicability domain, human intestinal absorption, blood-brain barrier, and human oral bioavailability, were observed. The profile was used to determine the properties of each inhibitor in order to examine the extent to which it will work as a drug candidate. 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. We hypothesized that VAS2870 would be the most effective inhibitor in silico due to its potency to NOX2, not present in the other inhibitors. 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. VAS2870 and apocynin were the most potent NOX2 inhibitors, and all four inhibitors 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 developing drugs to treat ischemic stroke.

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ischemic stroke ros nox inhibitor in silico