High Throughput Screening of Quorum Sensing Inhibitors Based Lead Molecules for Pseudomonas aeruginosa Associated Infections

Quorum sensing (QS) is a process of cell-cell communication in bacteria by the use of signalling molecules that bind to the receptor protein and directly or indirectly affect transcription and translation. QS proteins may be used as a drug target for the inhibition of signalling pathway to control bacterial cell population. In present study the QS protein LasR of Pseudomonas aeruginosa was used as druggable target. Total fifteen inhibitors of LasR in 32 conformations were used for high-throughput computational docking. On the basis of docking score and glide score suitable inhibitors were identified. These selected inhibitors can be used as lead molecules for the designing of inhibitor based drugs. Lead molecules were further characterised by ADMET analysis, which include Lipinski’s rule, Jorgensen’s rule, blood-brain barrier penetration, Skin permeability, Human intestinal absorption and oral absorption. [(4E)-1-hydroxy-3methylpyridin-4(1H)-ylidene]azinic acid] was found to be best inhibitor of LasR among all the inhibitors with best ADMET properties. In this study the above lead molecule was found to be a better alternative for the inhibition of bacterial population and in prevention in associated diseases. Present study focuses on the importance of structure based in silico drug design which takes less time and is cost effective.