In-silico Molecular Docking Studies of Methyl Oxadiazole Hybrids Inhibiting Acetylcholinesterase for Alzheimer’s Disease Treatment

Memory loss and cognitive decline are the main signs of Alzheimer’s disease (AD), a neurodegenerative brain illness that affects millions worldwide. AD is linked to aberrant beta-amyloid, low acetylcholine, oxidative stress, inflammation, and T protein aggregation. Low acetylcholine levels are one of the most important factors in Alzheimer’s disease since they are essential for cognitive processing and memory. This is why we’ve concentrated on ACHEIs and the cholinergic system. We used in-silico testing to find new and effective oxadiazole acetylcholinesterase inhibitors. This study created, docked, and predicted numerous novel oxadiazole scaffolds to find Alzheimer’s disease cholinesterase inhibitors. Offline tools like Protein Data Bank for PBD protein file downloads and Marvin Sketch for chemical structure representation enhance internet resources like PubChem, Swiss ADMET, and PyRx 0.9 for molecular docking research. We used Swiss Protein Data Bank Viewer for protein synthesis and https://plip-tool.biotec.plip.index.html for active site pocket prediction. Study results suggest 108 oxadiazole hybrids were used. Most compounds had zero or one Lipinski rule of five (RO5) violation. ADME research shows that all of these medicines have perfect pharmacokinetic features, including blood-brain barrier penetration. The docking tests demonstrate that our compounds have high target receptor binding energies of 8.1 to 12.3 kcal/mol. Similar to donepezil (12.76 K/cal), 2, 19, and 36 had 12 kcal/mol binding energies, 4, 11, and 32 had 11.5 kcal/mol, while compound 18 had 12.7 kcal/mol. Finally, our medications highly react with amino acid residues like Arg393, Arg525, Ala528 Asp400, and others. This binding approach is similar to donepezil, the gold standard. ADMET projections suggest these medications will have safer toxicological and pharmacokinetic profiles. The research aims to produce innovative AChE medications that restore brain acetyl choline levels, relieve Alzheimer’s disease symptoms and promote cognitive development.