Innovative Design, Synthesis, and In Silico Evaluation of Bis-Ureido Substituted Antipyrine Derivatives: Molecular Modeling and ADME Insights

Authors : Süleyman Akocak

Pages : 264-278

Doi:10.21597/jist.1591716

View : 42 | Download : 24

Publication Date : 2025-03-01

Article Type : Research Paper

Abstract :Molecular docking is a computational modeling technique that predicts the interactions between molecules of interest and certain protein structures. This approach estimates binding affinities and visualizes bond interactions, making it a useful tool for drug discovery. Molecular docking helps to rationally design new therapeutic medicines by offering insight into potential binding connections between molecular structures prior to laboratory testing. ADME investigations supplement molecular docking by assessing the pharmacokinetic features of the examined compounds, consequently determining their eligibility as possible therapeutic candidates. In this study, we show the creative design, synthesis, and In silico evaluation of a novel series of bis-ureido substituted antipyrine derivatives, with a focus on their potential as cholinesterase inhibitors. Using molecular modeling tools, we combined the bis-ureido group with the antipyrine drug to improve the pharmacological properties of these molecules. The newly synthesized compounds were comprehensively characterized by spectroscopic approaches, including FT-IR, ¹H-NMR, and ¹³C-NMR, followed by molecular docking experiments to analyze their interactions with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Additionally, In silico ADME assessments were performed to determine the compounds\\\' pharmacokinetic characteristics and drug-likeness properties. Notably, compound 10 showed strong binding affinities against AChE and BChE, with binding energies of -14.47 and -11.75 kcal/mol, respectively. The docking data revealed high binding affinities, indicating a significant inhibitory potential for both AChE and BChE. This study points out the need of combining molecular docking and ADME investigations in contemporary pharmaceutical design and development.
Keywords : Antipirin, In siliko, ADME, Bis-üreido, Antikolinesteraz

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