In silico Analysis of Inhibitory Potential of Major non-Steroidal Anti-inflammatory Drugs against Las-quorum Sensing Circuit in Pseudomonas aeruginosa

The emergence of drug resistance, therapeutic failure, and the development of Pseudomonas aeruginosa infections are primarily attributed to biofilm formation and quorum sensing (QS) dependent virulence factors. The antimicrobial potential of some non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, has been determined in laboratory studies. Herein, a docking analysis was conducted to examine the interaction between seven NSAIDs and the proteins of the Las system. Initially, the three-dimensional structure of selected NSAIDs (Diclofenac sodium, Ibuprofen, Ketoprofen, Mefenamic acid, Meloxicam, Naproxen, and Tenoxicam), and natural ligand of LasR (۳-oxo-C۱۲-HSL) were retrieved from PubChem database. Also, crystal structures of LasI Synthase and transcriptional activator protein LasR were obtained from Protein Data Bank. Subsequently, the molecular docking analysis utilizing AutoDock Vina software was employed to investigate the capability of the selected NSAIDs to inhibit the LasI/LasR receptor. Based on our findings, the majority of the selected NSAIDs exhibited favorable interactions with LasI/R proteins. Moreover, ketoprofen exhibited the strongest interactions with both proteins. In summary, this work suggested that NSAIDs, especially ketoprofen and naproxen, have promising potential as candidates for further in vitro and in vivo investigations to inhibit the QS circuits of P. aeruginosa.