Sulfonamide derivatives targeting urease: Structural diversity and therapeutic potential

Urease, a nickel-dependent metalloenzyme, plays a pivotal role in microbial survival, nitrogen metabolism, and the pathogenesis of urease-associated diseases, including
Helicobacter pylori
infections and urolithiasis. The excessive urease activity also contributes to soil alkalization and ammonia volatilization, leading to significant environmental and agricultural concerns. Inhibiting urease has emerged as a promising strategy to combat bacterial resistance and improve agricultural sustainability. Among the diverse classes of urease inhibitors, sulfonamide-containing molecules have gained substantial attention due to their structural versatility, bioavailability, and potent inhibitory activity. Recent advancements in computational approaches, including molecular dynamics simulations and quantum chemical studies, are also addressed to enhance the predictive capabilities of inhibitor design. The key objectives of this review are to comprehensively compile sulfonamide-containing compounds reported as urease inhibitors, analyze their structure-activity relationships (SAR), highlight the most potent derivatives based on IC
50
values, and provide insights from molecular docking and mechanistic studies to support future drug design efforts. This comprehensive review emphasized bridging the gap between fundamental urease inhibition studies and translational research, paving the way for developing next-generation urease inhibitors with improved efficacy and selectivity.