Assessment of Some Aminoglycoside Drugs Repurposing as Helicobacter pylori Urease Enzyme Inhibitors by In silico and In vitro

Background: A Helicobacter pylori is a Gram negative bacterium associated with gastrointestinal tract disease. Helicobacter pylori can grow in extreme acidic condition like stomach under microaerobic conditions. The bacterium colonizes the antrum of the stomach, causing gastritis and peptic ulcers. The urease enzyme produced by H. pylori is essential for bacterial survival in the acidic stomach environment, making it a target for drug therapy. Objective: This study aims to assess of some aminoglycoside approved drugs including paromomycin sulfate, tobramycin, gentamicin, amikacin, and capreomycin sulfate as H. pylori urease inhibitor in order to prevent catalysis action of urease to convert urea to ammonia by using of molecular docking. Materials and Methods: Virtual screening was performed to identify potential H. pylori urease inhibitors. Molecular docking simulations were conducted using the Glide software, and several compounds from the zinc15 database were analyzed concerning in silico . Among the top-ranked compounds, paromomycin, tobramycin, amikacin, capreomycin, and gentamycin exhibited strong binding affinity to the H. pylori urease protein. The inhibitory effect for purified urease was performed by using drug candidate to bind in active site of urease. Also inhibition of urease enzyme in vitro H. pylori isolation, diagnosis by using PCR (polymerase chain reaction). Inhibition of urease by aminoglycosides demonstrate a clear dose-dependent response for local strain increasing concentration of aminoglycosides caused gradual decrease in urease activity for local strain. Results: In silico results of molecular docking indicate that the aminoglycoside which includes paromomycin, amikacin, gentamicin, tobramycin, and capreomycin can bind to urease enzyme at active site. The experimental results indicate that paromomycin, amikacin, gentamicin, tobramycin, and capreomycin have inhibitory effects on urease activity. Results demonstrated dose-dependent inhibition of urease activity by the drugs, with a difference of IC50 for each drugs, respectively. There was a significant difference at P ≤ 0.05 between the inhibitory performance on local compared to reference strain. Conclusion: Aminoglycoside emerges as a promising urease inhibitor for H. pylori infection. Molecular docking regarding the relatively highest affinity toward to the H. pylori urease, and in vitro studies provide valuable insights for potential drug development against H. pylori -induced gastrointestinal diseases. Further research is needed to explore the clinical efficacy of capreomycin, paromomycin, amikacin, gentamicin, tobramycin in managing H. pylori infections and have antimicrobial activity and direct anti-urease effect on urease produce by H. pylori .