In silico,neuroprotective effect of phenyl-methanol based benzylidenehydrazineyl derivatives by scavenging reactive oxygen species via sirtuin 3 in Parkinson's disease

Abstract

Background Parkinson's disease has been extensively treated with phenyl-based compounds. Various in vivo investigations on phenyl-based derivatives have demonstrated a neuroprotective effect against Parkinson's disease by reducing reactive oxygen species and oxidative stress via the activation of the sirtuin 3. Using a network pharmacology approach, this study intends to evaluate the possible function of phenyl-based derivatives as an anti-Parkinson agent. Materials and Methods The compilation of phenyl-based derivatives utilized numerous open-source databases. The developed compounds were subjected to virtual screening by the hypothesized targets implicated in the development of Parkinson's disease. The drug-likeness score, ADMET profile, and potential adverse effects of the designed ligands were also predicted. Using the Kyoto Encyclopedia of Genes database, the regulated pathways were modeled (KEGG). Based on the number of edge counts, the network between compounds, genes, and pathways with the most modifications was found. Schrödinger suite 2022 was used to undertake the molecular docking and molecular dynamics investigation (100 ns) for the most modulated designed ligand with protein. Results It was discovered that phenyl-based derivatives alter the proteins implicated in the progression of Parkinson's disease. In this study, BZ-1 had the highest number of edge counts and node counts modulating the FOXO1 gene and FOXO signaling pathway.BZ-1 and resveratrol were discovered to have docking scores of -7.936 kcal/mol and − 4.28 kcal/mol, respectively, with an MMGBSA score of -58.77 and − 48.97, respectively.