Evaluation of Physicochemical Parameters Influencing Bioavailability and Therapeutic Potential in Nucleoside Analogues

Abstract

This research systematically investigates the physicochemical properties of novel nucleoside analogues, highlighting their molecular weight, lipophilicity (LogP), solubility, topological polar surface area (TPSA), drug-likeness, bioavailability, and hydrogen bonding characteristics. Computational tools, including SwissADME and ChemAxon, were employed to predict and analyze these essential parameters. The findings demonstrate optimal molecular weight ranges, moderate lipophilicity, and varied solubility profiles, significantly influencing the potential pharmacokinetic and pharmacodynamic profiles of the developed compounds. Our analysis revealed that compounds such as O4-Methylthymidine and 5-Fluorouridine exhibited optimal physicochemical profiles, including high solubility (9.87 mg/mL and 8.02 mg/mL, respectively), moderate lipophilicity (LogP 0.97–2.43), and favourable TPSA values (≤ 100 Ų), suggesting high potential for oral bioavailability. Notably, six compounds complied with Lipinski’s Rule and five met Veber’s rule, indicating strong drug-likeness. However, AMP-γ-S and 6-Thioguanosine exhibited low bioavailability (0.13 and 0.14, respectively), warranting further formulation development.