Siberian Federal University

Nucleoside precursors and nucleoside analogs are gaining recognition as potential therapeutic agents in the development of therapies for neurodegenerative illnesses, including Alzheimer’s disease (AD). This study presents newly designed uridine analogues and selected marketed antifungal and antibacterial medications via an in silico process to determine their thermal stability, bioactivity, and therapeutic potential. The crystal structure of human acetylcholinesterase (PDB ID: 7E 3D) in association with tacrine as the target receptor was used for molecular docking investigations. To determine how strongly they bind, we looked at residues around the active- site gorge, such as ARG296, VAL294, PRO235, and THR 238. AutoDock Vina, which was used for docking, showed good binding energies and strong interaction patterns. The derivatives showed promising results for altering the function of acetylcholinesterase. Uridine and its analogs not only have neuroprotective effects but also function well against bacteria and fungi. This makes them good candidates for drug discovery because they can be used as multifunctional drugs. PASS prediction further proves the antibacterial ability of these materials. Additionally, in silico ADMET analysis revealed that the drugs had good pharmacokinetic properties, and density functional theory (DFT) calculations showed how their frontier molecular orbitals (FMOs), electrostatic potential distributions (ESPs), and thermodynamic stability work. Collectively, these computational findings highlight uridine derivatives and repurposed antimicrobial agents as promising candidates for further exploration in the context of Alzheimer’s disease therapy