In Silico Analysis of Antioxidant Phytochemicals with Potential NADPH Oxidase Inhibitory Effect

Abstract

Objective: NADPH oxidase (NOX) is known to produce reactive oxygen species (ROS) at physiological concentrations. However, it can be over-activated with some disease conditions and produces excess ROS. Several molecules have shown an ability to suppress the enzyme’s over-activity, although some weaknesses have been found. Hence, the attempt to screen phytochemicals, with the aim of finding the most specific and effective NOX inhibitor. Material and Methods: The study was carried-out via an in-silico approach. First, phytochemicals with antioxidant activity, according to the literature review, were selected and downloaded from the PubChem database in SDF files. NOX with PDB: 2CDU was downloaded from the protein databank. Drug-likeness properties and biological activities were predicted using ADMETMESH and the Predict Activity Spectra of Substances (PASS) software. Phytochemical-NOX interactions were performed via molecular docking, whereas, docked conformations and bond residue amino acids were analyzed using Protein-plus software. Results: The result of this study predicted 13 phytochemicals with drug-likeness properties, out of which 9 showed NOX-inhibitory activity. Docking results predicted all of the 9 phytochemicals were capable of interacting with NOX, by binding to at least one amino acid. The reference inhibitor (Apocynin, -8.3 kcal/mol) and some phytochemicals (caffeic, eriodictyol, hesperetin, and morin with ΔG -6.1 to -7.7 kcal/mol) were predicted to have bonded to Ser115, via hydrogen bonding. On the other hand, epicatechin gallate and quercetin with ΔG −8.7 and −8.1 kcal/mol did not bind to Ser115, but rather through other amino acids. Conclusion: This study has led to the prediction of phytochemicals with NOX-inhibitory effects, which could be considered for further study.