In Silico Design and Functional Annotation of Nitrogenous Base-Modified Nucleosides for Therapeutic Applications

Abstract

Nucleoside analogues are a cornerstone in the treatment of viral infections, cancers, and metabolic disorders, with modifications to their nitrogenous bases offering routes to enhanced efficacy and specificity. This study presents the in-silico design and functional annotation of a novel series of nitrogenous base-modified nucleosides, structured into purine-based, pyrimidine-based, and specially modified therapeutic categories. Utilizing cheminformatics tools and SMILES-based molecular representations, twelve compounds were computationally modelled and annotated for their potential therapeutic roles, including cytotoxic, immunogenic, antimetabolite, and epigenetic applications. The design incorporates known bioactive motifs, such as thiol, halogen, and methyl substitutions, to guide future docking and drug-likeness evaluations. Results suggest that these analogues present promising candidates for targeted docking against disease-relevant proteins and justify further studies into their biological efficacy.