Comparative molecular docking and ADMET profiling of niclosamide and berberine against multiple Helicobacter pylori enzymatic targets

Objectives : The eradication of Helicobacter pylori is often challenged by antimicrobial resistance, adherence issues, and regional variation in treatment outcomes. As a hypothesis-generating step, early-stage pharmaceutical prioritization can identify repurposed or bioactive structures for experimental testing. This study compared the docking profiles of niclosamide and berberine against selected H. pylori enzymatic targets, using levofloxacin as a clinically relevant antibacterial comparator. Materials and methods : Blind molecular docking was performed against H. pylori urease, DNA gyrase subunit A, and shikimate kinase. Top-ranked poses were described using Vina-type scores, three-dimensional binding inspection, two-dimensional residue-interaction mapping, and absorption, distribution, metabolism, excretion, and toxicity (ADMET)/drug-likeness predictions. Docking scores were treated as ranking scores rather than binding free energies or experimental affinity constants. Results : In this small docking matrix, berberine produced the most negative descriptive mean score, while niclosamide produced one of the two top-ranked urease poses. These score differences do not establish differences in binding affinity, target engagement, or biological potency. Levofloxacin was included as a clinically relevant comparator. Predicted ADMET descriptors highlighted compound-specific questions related to exposure, solubility, and formulation but were not interpreted as evidence of therapeutic suitability. Conclusion : The integrated analysis prioritizes niclosamide and berberine for further anti- H. pylori investigation without demonstrating binding, enzyme inhibition, antibacterial activity, or therapeutic efficacy. The predicted poses and scores, considered alongside existing experimental literature and predicted ADMET descriptors, define testable hypotheses for urease inhibition assays, minimum inhibitory concentration (MIC) determination, cytotoxicity testing, and formulation-focused studies.