Targeting Urease: A Promising Adjuvant Strategy for Effective Helicobacter pylori Eradication

Helicobacter pylori, a Gram-negative bacterium, exhibits unique adaptations to thrive in an acidic gastric environment. Urease enzyme present in the bacteria converts urea to ammonia and carbon dioxide, making the surrounding acidic environment of the bacteria neutral. This adaptation helps the bacteria to survive and travel further to gastric epithelial cells, where it attaches to mucin and damages the tissues, leading to gastritis, peptic ulcer, and ultimately, cancer. Physicians typically prescribe first-, second-, and third-line antibiotic therapies to eliminate the bacterium, but these treatments frequently fail to achieve complete eradication. This failure, driven by factors such as the coccoid form, high bacterial load, and biofilm formation, contributes to the growing problem of antibiotic resistance. Targeting urease activity presents a promising strategy to reduce the H. pylori pathogenicity and enhance its susceptibility to antibiotics. Inhibiting urease enzyme activity would be an option to make the bacteria less pathogenic and more prone to antibiotic treatment. Including the urease inhibitors as an adjuvant with the current antibiotic treatment regimen would effectively eradicate the bacteria. This comprehensive review discusses the structural characteristics of the urease enzyme and its role in pathogenesis and the available urease inhibitors along with their pharmacophoric features. An elaborative pharmacophore-based screening and docking study on scaffolds such as chlorogenic acid, catechol, and hydroxamic acid to discover a potent urease inhibitor is a future scope identified in this review.