Aromatic secondary metabolite interactions with nickel-dependent urease

Aromatic secondary metabolites, hydroxybenzoic acids (HBAs)-β-resorcylic (2,4-dihydroxybenzoic acid) and gallic acid (3,4,5-trihydroxybenzoic acid)-constitute a class of phenolic compounds with numerous bioactivities that are of pharmacological and therapeutic interest. Urease plays a critical role in various biological pathways, with its activation linked to medical conditions including nephrolithiasis and peptic ulcers. The pursuit of potent and safe urease inhibitors has become a key priority in the field of pharmaceutical research. The present study sought to explore the molecular interactions between HBAs and urease to better understand their binding behavior. To assess the impact of both HBAs on the structural integrity and enzymatic activity of urease, fluorescence spectroscopy, FTIR, and molecular docking were utilized. Both HBAs quenched urease fluorescence through static mechanisms and bound favorably to the Ni²⁺-centered catalytic site. In silico ADME and toxicity profiling confirmed their drug-likeness and low predicted toxicity. Gallic acid exhibited stronger antioxidant and urease inhibition activity than β-resorcylic acid, highlighting the importance of hydroxyl substituents in radical scavenging. These findings suggest HBAs as promising natural scaffolds for developing dual-function urease inhibitors with antioxidant potential.