In silico development of new candidate of NADPH oxidase inhibitor for hypertension treatment

Abstract

Abstract Hypertension is a silent killer that becomes the important risk factor for stroke and ischemic heart disease. Oxidative stress which results from high production of reactive oxygen species (ROS) in the endothelial layer, contributes to hypertension pathophysiology. The high activity of NADPH oxidase is the main ROS source. Many medicinal plants have been developed to treat some human diseases. This study aimed to explore virtually Indonesian phytochemicals as a NADPH oxidase inhibitor for hypertension treatment. This bioinformatics study used a molecular docking method with P47-phox protein and apocynin as protein target and standard ligand respectively, which were obtained from Protein Data Bank and ZINC databases with 1NG2 and 0162515 codes. Indonesian phytochemicals were obtained from the HerbalIBD, had molecular structure from the PubChem database, and met the Lipinski’s criteria. The AutoDock Vina version 1.1.2 was used to analyse the binding affinity and sites and the PyMol 1.3 program was for visualization of molecular docking results. Apocynin interacted with P47-phox with -5.5 kcal/mol binding score and binding at Asp221, Arg302, Arg316 residues to prevent NADPH activation. Compared to apocynin, morindone had lower binding score (-7.7 kcal/mol) to bind to P47-phox and had similar binding sites at Arg 302, Arg 316, and Arg 318 residues. In conclusion, morindone potentially becomes a NADPH oxidase inhibitor in silico for hypertension treatment.