Identification of novel potential anti-quorum sensing molecules against LasR of Pseudomonas aeruginosa using in silico approach

Quorum sensing (QS), commonly known as inter-and intracellular communication in bacteria, is accomplished by small, diffusible signaling molecules termed as autoinducers. Numerous virulence factors that are involved in pathogenesis are regulated by QS. It has come to attention as a result of the growing resistance of bacteria to conventional antibiotics, as it applies less to no selective pressure to limit the development of resistance among bacteria. For inhibitors, LasR, a transcription factor that regulates QS in Pseudomonas aeruginosa, is a promising therapeutic target. Hence, the objective of this study is to identify possible LasR inhibitors from natural substances. Virtually 2068 ZINC database compounds were tested against the LasR structure. Following the filtering of suitable compounds using Lipinski’s rule and ADME criteria. Depending on binding energy, eight novel potential QS inhibitory agents were identified. To determine how inhibitors and targets bind, structures of LasR-ligand complexes were examined. It is important to note that all of the compounds are structurally distinct from 3-oxo-C₁₂-HSL, a native autoinducer of LasR, which is essential for the activation of LasR dimer that regulates QS system in Pseudomonas aeruginosa. These inhibitors are natural in origin and hence can be very useful in treating Pseudomonas infection; however, we have to properly evaluate their effectiveness, safety, and mode of action, through in vivo and in vitro investigation.