In Silico Investigation of Dual‐Target Quorum Sensing Inhibitors to Eradicate Biofilm Formation in Candida albicans

Candida albicans ( C. albicans ) is an opportunistic yeast that forms biofilms, which confer increased resistance to antifungal agents, making infections very difficult to treat. One of the mechanisms regulating this virulence is quorum sensing (QS), which can be defined as a cellular communication mechanism based on the production of autoinducer, namely, farnesol. We previously reported that the essential oils of Cistus ladanifer , Matricaria chamomilla , and Pistacia lentiscus inhibit C. albicans . In this context, a virtual screening of 48 molecules derived from these plants, as well as their ADMET property predictions, was undertaken to identify the most promising ligands for inhibiting QS receptors (CYC and RAS1) compared to farnesol. The latter exhibited a binding affinity of −7.0 kcal/mol for both CYC and RAS1. Two phytomolecules, namely, chamazulene and γ ‐muurolene, exhibited stronger binding affinities of −7.6 and −8.1 kcal/mol, respectively, for CYC, while toward the RAS1 receptor, they showed identical binding affinities of −7.1 kcal/mol. According to the binding free energy calculations performed using Prime MM‐GBSA, the complexes formed by γ ‐muurolene exhibited high stability, maintained by coulombic, lipophilic, and Van der Waals interactions, demonstrating that γ ‐muurolene is a promising inhibitor of QS. Molecular dynamic simulations confirmed the conformational stability of the CYC‐ γ ‐muurolene and RAS1‐ γ ‐muurolene complexes, characterized by low RMSD values, suggesting favorable dynamic behavior. The results as a whole provide a solid foundation for further experimental validation.