Exploring propolis-derived compounds as quorum sensing inhibitors for Candida albicans: a molecular docking and...

The opportunistic fungal pathogen Candida albicans (C. albicans) employs quorum sensing (QS) to regulate virulence factors such as biofilm formation and morphological switching. Targeting QS offers a promising approach to attenuate pathogenicity without promoting resistance. The objective of the present study was to computationally screen a library of 106 propolis-derived compounds to identify natural quorum-sensing inhibitors targeting the CYC and RAS1 receptors. Advanced techniques, including molecular docking, molecular dynamics (MD) simulations, and ADMET predictions, were employed to establish a workflow for structure-based virtual screening. Farnesol, used as a reference compound, showed a good binding affinity (-7.0 kcal/mol) toward CYC and RAS1 receptors. Two propolis flavonoids, kaempferol-3-O-4-O-p-coumaryl-glucoside (KCG) and isorhamnetin-3-glucoside-7-rhamnoside (IGR), exhibited stronger binding affinities with CYC and RAS1 receptors (between - 8.4 and - 10.3 kcal/mol). Based on Prime MMGBSA binding free energy calculations, the RAS1-KCG complex demonstrated the most favorable interaction, driven by significant coulombic and Van der Waals contributions. The CYC-KCG complex also showed relatively strong binding. These results highlight the potential of KCG as a versatile inhibitor capable of interacting with both targets. MD simulations further confirmed the excellent conformational stability of both KCG-receptor complexes, as indicated by low RMSD values, suggesting favorable dynamic behavior. These findings provide a strong foundation for subsequent validation.