Computational Investigation of 5-Ethynyl-2’-deoxyuridine (EdU) as a Biologically Active Nucleoside Analogue: Insights from Molecular Docking, ADMET Profiling, and DFT Analyses

This study presents a comprehensive computational investigation of the molecule 5-ethynyl-2'-deoxyuridine (EdU), a thymidine analogue of considerable biological importance. The investigation includes quantum chemical analyses, molecular docking, and pharmacokinetic evaluation to assess the structural, electronic, and biological properties of EdU. Initially, the molecular geometry of EdU was optimized using Density Functional Theory (DFT), providing a basis for deeper electronic structure evaluations. Topological analyses, including Electron Localization Function (ELF) and Localized Orbital Locator (LOL), were performed to explore the distribution of electron density and bonding properties within the molecule. These visual and quantitative descriptors contributed to a clearer understanding of the reactivity and stability of the molecule. The pharmacokinetic behavior of EdU and its similarity to the drug was evaluated through in silico ADME (absorption, distribution, metabolism, and excretion) modeling. Using internet-based platforms such as SwissADME and admetSAR, various parameters were evaluated to determine the potential of the molecule as an orally active compound and its compliance with established drug similarity rules. Toxicological properties were further investigated using predictive tools to estimate acute and environmental toxicity risks. Molecular docking simulations were performed to investigate the interaction between EdU and the selected proteins alpha-amylase and alpha-glucosidase, selected for their endocrinological importance, providing insights into possible binding mechanisms and structural compatibility. Overall, this study uses a multidisciplinary computational approach to provide a detailed theoretical profile of EdU, contributing to the understanding of its chemical behavior and potential applications in biomedical research.