Computer-aided Analysis of Selective Phytochemicals as Potent Inhibitors of Parkin: Major Biological Target of Parkinson’s disease

Abstract

Parkinson's disease, caused by mutations in the Parkin that leads to loss of neuron is the second most widespread neurodegenerative disorder in the world. Phytochemicals are being considered due to their medicinal properties to cure many human diseases. The present study targets the inhibition of Parkin, a major biological target for Parkinson using 3150 phytochemicals from various medicinal plants. These plants are naturally growing in a local climate of Pakistan, India and China and being used for a long time for the medicinal purpose. A total of 3150 phytochemicals from various medicinal plants were collected for this in silico study. The pharmacological assessments prediction, molecular docking and density functional theory (DFT) based studies were done to fi nd out the latent inhibitory properties of these phytochemicals against Parkin. Out of 3150 phytochemicals, 175 showed human-suitable pharmacological properties and among those 175 compounds, 5 phytochemicals, i.e. Liquirtin, Shinfl avanone, Glabrone, GlycyrdioneB and IsoangustoneA to have potent inhibitory properties against Parkin and can be deliberated for additional in vitro and in vivo studies to evaluate their inhibitory eff ects against Parkin. They revealed binding affi nity greater than various previously reported inhibitors against Parkin. Additionally, DFT based analysis exhibited high reactivity for these fi ve phytochemicals in the binding pocket of Parkin, based on E LUMO , E HOMO and band energy gap. A total of 5 out of 175 phytochemicals are reported as highly potent inhibitors against Parkin which are liquirtin, Shinfl avanone, Glabrone, Glycyrdione B and IsoangustoneA from the same medicinal plant Glycyrrhiza glabra. However, these 5 phytochemicals can be considered for further in vivo and in vitro analysis for the clinical development of a drug against the world's second most common brain disorder, the Parkinson's disease.

Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling

“…Parkin has a functional role in E3 ubiquitin-protein ligase and mediates the mitophagy process [ 42 ]. The targeting of parkin could provide therapeutic effects on neurodegenerative disorders [ 43 ]. In comparison, we studied the binding affinity of mavoglurant, an anti-Parkinson drug [ 44 ], which was reported to inhibit parkin activity [ 43 ].…”

“…The targeting of parkin could provide therapeutic effects on neurodegenerative disorders [ 43 ]. In comparison, we studied the binding affinity of mavoglurant, an anti-Parkinson drug [ 44 ], which was reported to inhibit parkin activity [ 43 ]. The molecular docking results show that mavoglurant capably docked into the catalytic domain of parkin with a binding energy of −5.4 kcal/mol.…”