j. nat. appl. sci. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi 1308-6529 Süleyman Demirel University 10.19113/sdufenbed.1895776 Organic Chemical Synthesis Computational Chemistry Organik Kimyasal Sentez Hesaplamalı Kimya Aril ve Aroil Hidrazon İçeren Heterosiklik Fenolik Bileşiklerin Antioksidan Potansiyelinin İncelenmesi: İn Vitro ve Teorik Araştırmalar Exploring the Antioxidant Potential of Heterocyclic Phenolic Compounds with Aryl and Aroyl Hydrazones: In Vitro and Theoretical Investigations https://orcid.org/0000-0003-1409-782X Dilek Ömer ISPARTA UYGULAMALI BİLİMLER ÜNİVERSİTESİ, REKTÖRLÜK 04 24 2026 30 1 228 242 02 23 2026 04 02 2026 Copyright © 1995, Süleyman Demirel University Journal of Natural and Applied Sciences 1995 Süleyman Demirel University Journal of Natural and Applied Sciences

Bu çalışma, çeşitli heterosiklik fenollerin radikal süpürücü ve indirgeme potansiyellerinin deneysel ve hesaplamalı yaklaşımların birlikte kullanıldığı kapsamlı bir değerlendirmesini sunmaktadır. Radikal süpürücü ve indirgeme potansiyelleri DPPH ve CUPRAC deneyleri ile belirlenmiş; etki mekanizmasını aydınlatmak amacıyla moleküler kenetleme, MM/PBSA enerji değerlendirmeleri ve moleküler dinamik simülasyonlarından elde edilen atomistik düzeydeki bulgularla desteklenmiştir. Test edilen bileşikler arasında, üç fenolik hidroksil grubu taşıyan bileşik 5 üstün antioksidan performans göstermiş ve TEAC değerleri CUPRAC için 7,85, DPPH için ise 3,60 olarak elde edilmiştir. Hesaplamalı sonuçlar deneysel verilerle tam uyum göstermiş ve bileşik 5’in en güçlü bağlanma afinitelerine sahip olduğunu ortaya koymuştur; özellikle MM/PBSA bağlanma serbest enerjileri 2C9V ve 1GTA için sırasıyla -86,19 kcal/mol ve -24,08 kcal/mol olarak belirlenmiştir. Öngörülen bağlanma modunun kararlılığını daha ileri düzeyde doğrulamak amacıyla 2C9V-5 kompleksi için 100 ns’lik bir MD simülasyonu gerçekleştirilmiş ve kompleksin simülasyon süresi boyunca dinamik ve yapısal kararlılığını koruduğu doğrulanmıştır. Toplu olarak değerlendirildiğinde, bu bulgular bileşik 5’i umut verici bir öncü antioksidan aday olarak tanımlamakta ve rasyonel antioksidan keşfi için deneysel ve hesaplamalı yaklaşımların birlikte kullanılmasının etkinliğini ortaya koymaktadır.

Abstract: This study presents a comprehensive evaluation of the radical scavenging and reducing potentials of various heterocyclic phenols through a combined experimental and computational approach. The radical scavenging and reducing potentials were determined through DPPH and CUPRAC experiments, which were further supported by atomistic insights from molecular docking, MM/PBSA energy assessments, and molecular dynamic simulations to clarify the mechanism of action. Among the tested compounds, compound 5, bearing three phenolic hydroxyl groups, displayed superior antioxidant performance, yielding TEAC values of 7.85 (CUPRAC) and 3.60 (DPPH). The computational results were in full agreement with the experimental data, showing that compound 5 attained the strongest binding affinities; specifically, its MM/PBSA binding free energies were determined as -86.19 kcal/mol and -24.08 kcal/mol for 2C9V and 1GTA, respectively. To further validate the stability of the predicted binding mode, a 100 ns MD simulation was conducted for the 2C9V-5 complex, confirming its dynamic and structural stability throughout the simulation. Collectively, these findings identify compound 5 as a promising lead antioxidant and demonstrate the effectiveness of combining experimental and computational approaches for rational antioxidant discovery.

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