Molecular docking, dynamics simulation and pharmacokinetic studies of Cyperus articulatus essential oil metabolites as inhibitors of Staphylococcus aureus

Cyperus articulatus has been extensively studied for its essential oil (EO), active components and antibacterial activities against a wide range of bacteria such as Bacillus megaterium, Streptococcus pyogenes, Staphylococcus epidermidis, Escherichia coli and Staphylococcus aureus. However, knowledge of the biomolecular interaction of the individual EO metabolites responsible for its inhibition activities is lacking. The multi-drug-resistant bacteria S. aureus, which is of prime concern, has been reported to be inhibited by Cyperus articulatus rhizome EO. The present work analyzed the molecular interactions of the major Cyperus articulatus rhizome EO metabolites with the target enzyme TyrRS of S. aureus and studied the conformational dynamics and stability of the protein-ligand complexes. Molecular docking studies of selected EO metabolites such as mustakone, longifolenaldehyde, cyperotundone, α-copaene, β-calacorene, α-calacorene and khusinol were conducted along with standard drug chloramphenicol for comparative analysis of their binding affinity with S. aureus TyrRS. The metabolites khusinol, mustakone, β-calacorene and α-calacorene generated comparable docking scores (−6.4, −6.2, −6.1 and −6.2 kcal/mol, respectively) with that of the drug chloramphenicol (−6.3 kcal/mol). Most EO metabolites did not exhibit H-bonding with the S. aureus TyrRS residues and were stabilized through pi-interactions. The MD simulation study illustrated that compounds like mustakone could effectively bind to the receptors of S. aureus TyrRS with high stability and integrity. Pharmacokinetic, drug-like properties and toxicity analysis of the EO metabolites supported the candidature of mustakone and khusinol as pharmacologically important antibacterial drug ingredients. The study envisaged the structural framework of the EO metabolites for antibacterial drug design. Communicated by Ramaswamy H. Sarma