Identification of the potential phytocompounds from Endostemon viscosus against GAPDH : a computational approach

Oxidative stress is a phenomenon caused by an imbalance between the production and accumulation of reactive oxygen species (ROS) in cells and tissues and the ability of the biological system to detoxify these reactive products. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the most common targets of oxidative stress, and the oxidation of the enzymes causes the inactivation of Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the formation of disulfide bonds between molecules, leading to aggregates, and eventually to cell death. Inhibition of GAPDH enzymatic activity was due to the formation of a disulfide bond between Cys-149, Cys-152, and Cys-156, which forms a structural reorganization of GAPDH. In addition, Cys-152 specifically prevents oligomerization and aggregation of GAPDH by blocking the cysteine residue and counteracting its oxidative modifications. The present study aimed to investigate the chemical composition of methanolic solvent and the essential oil extracted from the aerial part of Endostemon viscosus by GC-MS, and to evaluate its antioxidant properties against Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) aggregation through molecular docking. The volatile chemical compounds were analyzed by gas chromatography-mass spectrometry (GC-MS), and the metabolites prepared for molecular docking analysis against the GAPDH protein were done using Schrödinger software. According to the results of molecular docking, DFT analysis, ADME and MD simulation for the compounds, p-Methoxyheptanophenone (methanolic extract) and sclareol (essential oil extract) interacted with Cys-152 residues with a better glide score and obtained fine stability through MD studies. Overall, the study suggests that the GC-MS compounds from the methanolic solvent and oil from Endostemon viscosus exhibited prominent antioxidant properties against GAPDH.

The online version contains supplementary material available at 10.1007/s40203-023-00183-z.