To, Editorial Office Applied Biochemistry and Biotechnology Screening Natural Compounds using Zinc 15 Database for Insilico Study of GSK-3β Inhibitors as anti-Alzheimer Potential

Abstract

Abstract Alzheimer's disease is a neurologic condition that predominantly afflicts the elderly, characterized by its progressive and multifaceted nature, and recognized as the primary global source of dementia. In 2019, Alzheimer's disease ranked as the 7th most common cause of death. In the year 2023, it is estimated that around 6.7 million Americans who are aged 65 and above are grappling with disease. AD poses a significant worldwide health challenge, demanding inventive methods for the discovery of new drugs. GSK-3beta plays a role in phosphorylating the tau protein, which is a central element in the formation of neurofibrillary tangles. The inhibition of GSK-3β presents a fresh approach to reducing the development of both amyloid plaques(Aβ) and neurofibrillary tangles, which are two key pathological hallmarks of AD. The exploration of natural compound databases through virtual screening represents a highly promising avenue in the pursuit of innovative Alzheimer's disease treatments. In this study, we have selected a natural product database derived from ZINC15. Initially, the 2,24,191 natural compounds underwent screening to assess their ability to meet BBB parameters and ADMET properties. Based on the results of ADMET analysis, the most promising compounds (4241) were chosen and subjected to docking studies using Auto Dock Vina. Subsequently, the top compounds were selected from the docking outcomes having binding scores higher than that of standard co-crystal ligand OH8 (-8.4 kcal/mol) and CNS MPO Score between 0 to 6. The molecular dynamics simulation results indicated that the compounds remained stable throughout the entire simulation duration, exhibiting improved (RMSD) and (RMSF) values compared to the standard ligand.