New NADPH Oxidase 2 Inhibitors Display Potent Activity against Oxidative Stress by Targeting p22^phox-p47^phox Interactions.

ABSTRACT: NADPH oxidase (NOX2) is responsible for reactive oxygen species (ROS) production in neutrophils and has been recognized as a key mediator in inflammatory and cardiovascular pathologies. Nevertheless, there is a lack of specific NOX2 pharmacological inhibitors. In medicinal chemistry, heterocyclic compounds are essential scaffolds for drug design, and among them, indole is a very versatile pharmacophore. We tested the hypothesis that indole heteroaryl-acrylonitrile derivatives may serve as NOX2 inhibitors by evaluating the capacity of 19 of these molecules to inhibit NOX2-derived ROS production in human neutrophils (HL-60 cells). Of these compounds, C6 and C14 exhibited concentration-dependent inhibition of NOX2 (IC₅₀~1 µM). These molecules also reduced NOX2-derived

SUBMITTER: Treuer AV 

PROVIDER: S-EPMC10376059 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature