Antibacterial activity analysis of kaempferol and its derivatives targeting virulence and quorum sensing associated proteins by in silico methods
Golak Majumdar, Shyamapada Mandal · The Microbe · 2025
Bacterial quorum sensing is a mechanism of cell-to-cell communication which is vital for their physiological, metabolic and virulence activity. Bacterial infection in humans caused pathogenesis linked to virulence gene expression through quorum sensing. This study explores the inhibition activity of Persicaria hydropiper derived kaempferol and its derivatives against quorum sensing related transcriptional activator protein (LasR/2UV0) and quorum sensing regulator (QscR/6CC0) from Pseudomonas aeruginosa . Alongside molecular docking of kaempferol and its 13 derivatives displayed −6.5 to −10.5 kcal/mol binding energy achieved through different bond interactions. The Lipinski’s rules of five and ADMET prediction justified the drug-likeness of the bioactive compounds tested. Among them, kaempferol, kaempferide, afzelin and kaempferol 3-arabinoside showed excellent efficacies against the target protein P. aeruginosa LasR, along with acceptable pharmacokinetics properties. The molecular dynamics simulation authenticated the conformational stability of docked complexes (2UV0-kaempferol and 2UV0-kaempferide) with RMSD (0.18, 0.17), RMSF (0.11, 0.10), radius of gyration (1.51, 1.50) nm and MMPBSA based binding free energy (ΔG) of complex 2UV0-kaempfeol, 2UV0-kaempferide and 6CC0-kaempferol were −20.57, −0.07 and −0.05 kcal/mol respectively. The results obtained from the study provided an excellent efficacy of studied small molecules against inhibition of bacterial quorum sensing mechanism, and suggest that the lead candidates might be utilized in the development of therapeutic drugs against bacterial infections by targeting LasR protein. • Kaempferol had favourable binding against bacterial quorum sensing proteins. • Molecular dynamics simulation authenticates stable protein-ligand complex formation. • MMPBSA Gibbs free energy of kaempferol against LasR and QscR was notable. • ADMET and Lipinski’s RO5 showed acceptable drug-like property of kaempferol.