Design, synthesis, and comprehensive evaluation of novel azo-linked heterocycles derived from a Sorafenib precursor as potent antioxidant agents: An integrated in vitro and in silico approach
Journal of the Indian Chemical Society, cilt.103, sa.6, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 103 Sayı: 6
- Basım Tarihi: 2026
- Doi Numarası: 10.1016/j.jics.2026.102672
- Dergi Adı: Journal of the Indian Chemical Society
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, EMBASE
- Anahtar Kelimeler: Antioxidant activity, Azo-linked heterocycles, CUPRAC assay, DFT, MD simulation
- Isparta Uygulamalı Bilimler Üniversitesi Adresli: Evet
Özet
The design and synthesis of azo-linked heterocyclic systems remain a compelling strategy for developing potent therapeutics against oxidative stress. In this study, a novel series of heterocyclic azo derivatives (3a–d) derived from the aniline precursor of Sorafenib scaffold was synthesized and characterized. The experimental findings were corroborated by DFT calculations to evaluate their structural and electronic properties. PES analysis of the lead candidate, 3a, confirmed its conformational stability, highlighting an optimal balance between structural rigidity and flexibility for biological recognition. Compound 3a exhibited the lowest HOMO-LUMO energy gap and highest electrophilicity among the series, indicating exceptional reactivity. In silico ADMEt profiling confirmed favorable pharmacokinetic properties and adherence to Lipinski's Rule of Five, without blood-brain barrier permeation. Furthermore, molecular docking and 100 ns MD simulations against Xanthine Oxidase revealed superior binding affinities and robust dynamic stability for 3a compared to the standard antioxidant Trolox. Finally, in vitro antioxidant evaluation using the CUPRAC method definitively identified 3a as the most potent candidate, displaying a ∼62% higher efficacy than the reference standard. These findings highlight 3a as a highly promising lead scaffold for future antioxidant therapies.