In-Silico Evaluation of Nonsteroidal Anti-inflammatory Drugs as Antimicrobial Agents Against MDR Urinary Tract Infections
Abstract
The growing antibiotic resistance in urinary tract infection (UTI) pathogens underscores the need for alternative treatment strategies. This study employed Density Functional Theory (DFT) and molecular docking to investigate the repurposing potential of five nonsteroidal anti-inflammatory drugs (NSAIDs) celecoxib, indomethacin, ketoprofen, piroxicam, and salsalate against the fimbrial adhesin protein of Proteus mirabilis (PDB ID: 6H2L). DFT calculations at the B3LYP/6-311G(d,p) level revealed distinct electronic properties: ketoprofen exhibited the largest HOMO–LUMO band gap (4.575 eV), indicating high chemical stability, while piroxicam displayed the smallest band gap (2.719 eV), suggesting enhanced reactivity. Electrophilicity indices ranged from 14.822 eV (celecoxib) to 19.031 eV (piroxicam), reflecting differential binding propensities. Docking studies showed that ketoprofen achieved the strongest binding affinity (−7.8 kcal/mol), forming three stable hydrogen bonds with residues THR80, LYS78, and HIS186. Indomethacin exhibited a binding affinity of −7.2 kcal/mol and the highest number of hydrogen bonds (four), while piroxicam displayed strong binding (−7.4 kcal/mol) with the shortest hydrogen bond distance (1.96 Å), highlighting its potential for stable protein interactions. Celecoxib and salsalate showed moderate binding affinities (−7.0 kcal/mol). Collectively, ketoprofen and piroxicam emerged as the most promising candidates for further evaluation. This study…
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