Molecular modelling and experimental validation of mangiferin and its related compounds as quorum sensing modulators of Pseudomonas aeruginosa

The LasR quorum sensing system regulates the virulence factors of Pseudomonas aeruginosa, a multi-drug resistant pathogen. Mangiferin and related compounds have been found to modulate this system as determined by in silico and in vitro experimental procedures. ZINCPharmer was used to compile a library of over 1000 metabolites that were screened to the top five based on shared pharmacophores and drug-like properties with mangiferin. Molecular docking and molecular dynamics simulation (140 ns) showed that ZINC E (− 55.64 ± 2.93 kcal/mol) and ZINC D (− 54.51 ± 2.82 kcal/mol) had significantly lower binding free energy compared to mangiferin-LasR (− 42.24 ± 3.94 kcal/mol) and the reference standard (azithromycin-LasR (− 40.01 ± 6.15 kcal/mol). ZINC D (95.16%) competed favorably with mangiferin (95.77%) as potential QS modulators at sub-minimum inhibitory concentrations relative to ZINC E (85.07%) and azithromycin (85.79%). These observations suggest mangiferin and related lead compounds as potential drug candidates for P. aeruginosa infection management.