In silico predictions of NADPH oxidase binding properties of selected flavonoids - Protective role in arsenic induced neurotoxicity

Abstract

The study was an attempt to provide evidence for the effect of selected flavonoids on NADPH oxidase (NOX), which is a key enzyme in the generation of oxidative stress. For this study, a set of flavonoids were selected and screened for their molecular properties like physicochemical descriptions, oral bioavailability, Blood-Brain Barrier (BBB) penetration and P-glycoprotein (Pgp) substrate property using Molinspiration online tool, Swiss ADME and Swiss Target Prediction websites. Based on the molecular properties, three flavonoids (Naringenin, hesperidin and diosmin) were narrowed down for further molecular docking studies as they were found to be Pgp substrates. The protein targets were duly selected as they are the subunits of the NOX subtype, which was commonly expressed in the brain and they are key elements of NOX activation. Molecular docking studies were carried out with Autodock vina software to enumerate the binding energies of the flavonoid molecules with the selected protein targets. The three flavonoids naringenin, hesperidin and diosmin, have shown good binding energies for the selected targets compared to apocynin, a well-known NOX inhibitor. The molecular docking results revealed that hesperidin had shown the highest bonding energies, followed by diosmin and naringenin. These flavonoids naringenin, hesperidin and diosmin, might be the better inhibitors of NOX and might usefully help in combating arsenic induced neurotoxicity. These in silico findings need further confirmation by in vitro and in vivo studies.