Density Functional Theory Investigation of Some Uridine Derivatives with Anti-Alzheimer Potential

Uridine is an important nucleoside involved in RNA biosynthesis and phospholipid metabolism in the brain. In the present study, uridine and several of its derivatives were theoretically investigated as potential inhibitors of Alzheimer's disease. The electron charge density at eight sensitive sites, including hydrogen acceptor atoms (N۱, O۴, O۵, and O۶) and hydrogen donor atoms (O۱, O۲, O۳, and N۲), was examined through the calculation and comparison of electric field gradients (EFGs) and nuclear quadrupole coupling constants (NQCCs). The results indicate that the presence of a phosphate group in compound ۳ increases the electron density at the O۱ atom compared with the other studied compounds. This finding is further supported by Natural Bond Orbital (NBO) analysis. The obtained results suggest that O۱ may act as the most active site in these compounds, and its electron density appears to be directly related to their biological activity. Therefore, any structural modification or substitution that increases the electron density at this atom may contribute to the development of more effective therapeutic agents for Alzheimer's disease. All calculations were performed using Density Functional Theory (DFT) at the B۳LYP/۶-۳۱G* level of theory. The HOMO–LUMO and molecular docking analyses consistently highlighted compound ۳ as the most promising derivative among the investigated compounds, exhibiting favorable electronic characteristics and the strongest predicted binding affinity toward AChE.

کلیدواژه ها:

Uridine ، Uridine monophosphate ، Alzheimer ، NQCCs ، NBO