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

Year 2025, Volume: 15 Issue: 2, 310 - 321, 31.08.2025

Meryem Alp

https://doi.org/10.5961/higheredusci.1697221

Abstract

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.

Keywords

5-Ethynyl-2’-deoxyuridine , DFT , Quantum chemical calculation , Topological analyses , Molecular docking

Biyolojik Olarak Aktif Bir Nükleozit Analoğu Olarak 5-Etinil-2’- deoksiüridin’in (EdU) Hesaplamalı İncelenmesi: Moleküler Yerleştirme, ADMETox Değerlendirmesi ve DFT Analizlerinden Elde Edilen Bilgiler

Abstract

Bu çalışma, kayda değer biyolojik öneme sahip bir timidin analoğu olan 5-etinil-2'-deoksiüridin (EdU) molekülünün kapsamlı bir hesaplamalı incelemesini sunmaktadır. Araştırma, EdU'nun yapısal, elektronik ve biyolojik özelliklerini değerlendirmek için kuantum kimyasal analizleri, moleküler yerleştirme ve farmakokinetik değerlendirme içermektedir. Başlangıçta, EdU'nun moleküer geometrisi Yoğunluk Fonksiyonel Teorisi (DFT) kullanılarak optimize edilmiş ve daha derin elektronik yapı değerlendirmeleri için bir temel sağlanmıştır. Elektron Lokalizasyon Fonksiyonu (ELF) ve Lokalize Orbital Konumlandırıcı (LOL) dahil olmak üzere topolojik analizler, molekül içindeki elektron yoğunluğu ve bağlanma özelliklerinin dağılımını keşfetmek için yapılmıştır. Bu görsel ve nicel tanımlayıcılar, molekülün reaktivitesinin ve stabilitesinin daha net anlaşılmasına katkıda bulunmuştur. EdU'nun farmakokinetik davranışı ve ilaca benzerliği, in silico ADME (emilim, dağılım, metabolizma ve atılım) modellemesi yoluyla değerlendirilmiştir. SwissADME ve admetSAR gibi internet tabanlı platformlar kullanılarak, molekülün oral olarak aktif bir bileşik olarak potansiyelini ve yerleşik ilaç benzerliği kurallarına uygunluğunu belirlemek için çeşitli parametreler değerlendirilmiştir. Toksikolojik özellikler, akut ve çevresel toksisite risklerini tahmin etmek için öngörücü araçlar kullanılarak daha fazla araştırılmıştır.
EdU ile endokrinolojik öneme sahip olduğu için seçilen alfa-amilaz ve alfa-glukosidaz seçil proteinleri arasındaki etkileşimi araştırmak için moleküler yerleştirme simülasyonları gerçekleştirilerek olası bağlanma mekanizmaları ve yapısal uyumluluk hakkında içgörüler sağlanmıştır. Genel olarak, bu çalışma EdU'nun ayrıntılı bir teorik profilini sunmak için multidisipliner bir hesaplama yaklaşımı kullanmakta, kimyasal davranışının ve biyomedikal araştırmalardaki potansiyel uygulamalarının anlaşılmasına katkıda bulunmaktadır.

Keywords

5-Etinil-2 , DFT , Kuantum kimyasal inceleme , Topolojik analiz , Moleküler yerleştirme çalışması

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