Virtual Screening of Potential Quorum Sensing Inhibitors of P. aeruginosa

  • Snigdha Bhardwaj [1]Department of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, Sam Higginbottom University of Agricultural, Technology and Sciences, Naini, Prayagraj, Uttar Pradesh, INDIA.[2]T.S College of Pharmacy, Murad Nagar, Ghaziabad, Uttar Pradesh (201206), INDIA.
  • Pushpraj S Gupta Department of Pharmaceutical Sciences, Faculty of Health and Medical Sciences, Sam Higginbottom University of Agricultural, Technology and Sciences, Naini, Prayagraj, Uttar Pradesh, INDIA.
Keywords: Drug-resistance, Pseudomonas aeruginosa, LasR protein, Quorum sensing inhibitor, Molecular docking, Lipinski’s rule.

Abstract

Background: Pseudomonas aeruginosa (P. aeruginosa) is considered as one of the most opportunistic pathogens that may infect humans and led to increase in bacterial virulence or pathogenicity. P. aeruginosa exhibits variety of virulence factors and their rate of expression are associated with cell-to-cell communication process also known as quorum sensing (QS). LasR, a transcriptional factor which regulates the process of QS in P. aeruginosa is known as attractive drug target. Materials and Methods: The research work involves identification of putative inhibitors of LasR by molecular docking approach. Total 60 compounds were docked in the active site of LasR and CviR protein, followed by subsequent screening based on Lipinski’s rule of five, Veber rule and molar refractivity. Results: Out of 60 compounds, total seven novel compounds were selected on the basis of binding energies (docking score> 10). Structures of LasRinhibitor complexes were analyzed to have vital insights from the binding between LasR and inhibitor molecules. The selected compounds were analyzed for physico-chemical properties and drug likeness to establish correlation between oral bioavailability and pharmacokinetics of compound. Conclusion: The study revealed the potential of thiazole derivative as novel QSI and expedite the possibility to combat virulence of multi-drug resistant P. aeruginosa in more effective manner.

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The docking pose of co-crystallized standard ligand (OHN) with LasR (PDB ID: 2UV0).
Published
2022-07-26
How to Cite
1.
Bhardwaj S, Gupta PS. Virtual Screening of Potential Quorum Sensing Inhibitors of P. aeruginosa. ijpi [Internet]. 26Jul.2022 [cited 5Dec.2022];12(3):260-71. Available from: https://www.jpionline.org/index.php/ijpi/article/view/1517