In silico identification of natural Alzheimer inhibitors targeting GSK-3β using receptor-based pharmacophore and molecular modeling studies

Abstract

The discovery of an ideal, and effective Alzheimer’s therapy is urgently required. The main pathological hallmarks of Alzheimer’s disease are neurofibrillary tangles, amyloid plaques, inflammation, and neuronal atrophy. Reports suggested Glycogen Synthase Kinase-3β is a promising target for exploring novel therapeutic regimens. The main objective of this study is to explore, and decipher natural inhibitors that can target GSK-3β protein effectively. The receptor-based pharmacophore modeling of GSK-3β protein was developed and screened against CNS-like natural databases. The final survival hits aligning accurately with the pharmacophoric features was assessed for molecular docking studies. Taking standard control of GSK-3β, Batatasin III, and Gigantol were confirmed as the best hits based on their binding free energies, molecular interactions, and optimal ADMET profiles. Our findings represent a promising starting point for developing novel natural regimens however rigorous testament is imperative through biological screening which is still underway.