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

Year 2025, Volume: 15 Issue: 1, 264 - 278, 01.03.2025

Süleyman Akocak

https://doi.org/10.21597/jist.1591716

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

Antipytine, In silico, ADME, Bis-ureido, Anticholinesterase

Bis-üreido Substitüe Antipirin Türevlerinin Yenilikçi Tasarımı, Sentezi ve İn Siliko Değerlendirilmesi: Moleküler Modelleme ve ADME Analizleri

Abstract

Moleküler docking, ilgi çekici moleküller ile belirli protein yapıları arasındaki etkileşimleri tahmin eden bir hesaplama modelleme tekniğidir. Bu yaklaşım, bağlanma afinitelerini tahmin eder ve bağ etkileşimlerini görselleştirir, bu da onu ilaç keşfi için faydalı bir araç haline getirir. Moleküler docking, moleküler yapılar arasındaki potansiyel bağlanma bağlantılarını laboratuvar testlerinden önce inceleyerek yeni terapötik ilaçların rasyonel tasarımına olanak tanır. ADME (Absorpsiyon, Dağılım, Metabolizma ve Eliminasyon) incelemeleri, incelenen bileşiklerin farmakokinetik özelliklerini değerlendirerek moleküler docking çalışmalarını tamamlar ve bu bileşiklerin potansiyel terapötik adaylar olarak uygunluğunu belirler. Bu çalışmada, bis-üreido grubu ile antipirin ilacını birleştirerek bu moleküllerin farmakolojik özelliklerini geliştirmeyi hedefleyen yenilikçi bir bis-üreido substitüe antipirin türevleri serisinin tasarımı, sentezi ve in silico değerlendirmesi sunulmaktadır. Yeni sentezlenen bileşikler, FT-IR, ¹H-NMR ve ¹³C-NMR gibi spektroskopik yöntemlerle kapsamlı bir şekilde karakterize edilmiş ve ardından asetilkolinesteraz (AChE) ve bütirilkolinesteraz (BChE) ile olan etkileşimlerini analiz etmek için moleküler docking deneyleri gerçekleştirilmiştir. Ayrıca, bileşiklerin farmakokinetik özelliklerini ve ilaç benzeri özelliklerini belirlemek için in silico ADME değerlendirmeleri yapılmıştır. Özellikle, bileşik 10, AChE ve BChE'ye karşı sırasıyla -14,47 ve -11,75 kcal/mol bağlanma enerjileri ile güçlü bağlanma afiniteleri göstermiştir. Docking verileri, hem AChE hem de BChE için önemli inhibitör potansiyelini ortaya koyan yüksek bağlanma afinitelerini işaret etmektedir. Bu çalışma, modern farmasötik tasarım ve geliştirme süreçlerinde moleküler docking ve ADME incelemelerinin bir arada kullanılmasının önemini vurgulamaktadır.

Keywords

Antipirin, In siliko, ADME, Bis-üreido, Antikolinesteraz

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