ABSTRACT Oxidative stress, driven by an imbalance between reactive oxygen species (ROS) and antioxidant defenses, contributes significantly to various pathological conditions and disorders. NADPH oxidase‐1 (NOX1), a key enzyme responsible for ROS production, is an attractive therapeutic target. Benzamide derivatives are promising scaffolds for developing multifunctional agents with antioxidant and enzyme inhibitory properties. The present study aimed to synthesize novel benzamide derivatives incorporating heterocyclic moieties and evaluate their potential antioxidant properties and NOX1 inhibition through in vitro and in silico approaches. Six benzamide derivatives (4a–4f) were synthesized using stepwise amide coupling and characterized via TLC, FTIR, 1 H NMR, 1 3 C NMR, and LC‐MS. Antioxidant activity was assessed by DPPH radical scavenging assay, with IC 50 values compared to vitamin C. Molecular docking was performed using Schrodinger Glide against the NOX1 protein (PDB ID: 7CFZ) to explore binding affinity and interaction profiles. Compound 4a showed the strongest antioxidant activity (IC 50 = 534.8 µg/mL). Docking studies revealed compound 4c exhibited the highest binding affinity (−5.978 kcal/mol) with key interactions involving Gln11, Val57, and Trp40. Other compounds also demonstrated favorable binding and hydrogen bonding interactions with active site residues of NOX1. These findings indicate that heterocyclic substitution enhances both antioxidant capacity and enzyme interaction.
B.S et al. (Thu,) studied this question.