Molecular Docking-Guided Repositioning of Non-Antibiotic Compounds as Potential Inhibitors of Staphylococcus aureus

Abstract

This study explores the repositioning of non-antibiotic drugs as potential inhibitors of Staphylococcus aureus; a clinically significant pathogen associated with antibiotic resistance. Molecular docking analysis was performed on 34 compounds targeting the tyrosyl-tRNA synthetase enzyme (PDB ID: 1JIJ), and 15 promising candidates were identified. Among these, six compounds—Meloxicam, Piroxicam, Quetiapine, Fluoxetine, Duloxetine, and Atorvastatin—were selected based on their strong binding affinity to key residues within the active site of the target protein. Initial in vitro evaluations at low concentrations (0.0002–0.0008 mg/mL and 5–20 mg/mL) did not yield significant antimicrobial effects. Consequently, four compounds were tested at higher concentrations (20–50 mg/mL). Piroxicam demonstrated consistent, dose-dependent antimicrobial activity at all concentrations tested, with inhibition zones in the range of 0.4 to 0.6 cm. Atorvastatin showed selective activity at 40 mg per ml, resulting in an inhibition zone of 0.7 cm. By contrast, fluoxetine and quetiapine did not show inhibitory activity at any concentrations. Positive results with Piroxicam and atorvastatin support the potential of repositioning drugs as a viable strategy for identifying new antimicrobial agents. By repurposing well-characterized, approved drugs, this approach offers a promising way to overcome conventional resistance mechanisms and help develop novel therapies in the global fight against antimicrobial resistance.