Staphylococcus aureus infections present a significant threat to the global healthcare system. The increasing resistance to existing antibiotics and their limited efficacy underscores the urgent need to identify new antibacterial agents with low toxicity to effectively combat various S. aureus infections. Hence, in this study, we have screened T-muurolol for possible interactions with several S. aureus-specific bacterial proteins to establish its potential as an alternative antibacterial agent. Based on its binding affinity and interactions with amino acids, T-muurolol was identified as a potential inhibitor of S. aureus lipase, dihydrofolate reductase, penicillin-binding protein 2a, D-Ala:D-Ala ligase, and ribosome protection proteins tetracycline resistance determinant (RPP TetM), which indicates its potentiality against S. aureus and its multi-drug-resistant strains. Also, T-muurolol exhibited good antioxidant and anti-inflammatory activity by showing strong binding interactions with flavin adenine dinucleotide (FAD)-dependent nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase, and cyclooxygenase-2. Consequently, molecular dynamics (MD) simulation and recalculating binding free energies elucidated its binding interaction stability with targeted proteins. Furthermore, quantum chemical structure analysis based on density functional theory (DFT) depicted a higher energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital (EHOMO-LUMO) with a lower chemical potential index, and moderate electrophilicity suggests its chemical hardness and stability and less polarizability and reactivity. Additionally, pharmacological parameters based on ADMET, Lipinski's rules, and bioactivity score validated it as a promising drug candidate with high activity toward ion channel modulators, nuclear receptor ligands, and enzyme inhibitors. In conclusion, the current findings suggest T-muurolol as a promising alternative antibacterial agent that might be a potential phytochemical-based drug against S. aureus. This study also suggests further clinical research before human application.

• Klíčová slova
• MD simulation, density functional theory, molecular docking, pharmacokinetics, phytochemicals,
• MeSH
• antibakteriální látky * farmakologie   chemie   MeSH
• antioxidancia farmakologie   chemie   MeSH
• bakteriální proteiny antagonisté a inhibitory   metabolismus   chemie   MeSH
• fytonutrienty * farmakologie   chemie   MeSH
• lidé MeSH
• objevování léků * metody   MeSH
• počítačová simulace MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• stafylokokové infekce farmakoterapie   mikrobiologie   MeSH
• Staphylococcus aureus * účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky * MeSH
• antioxidancia MeSH
• bakteriální proteiny MeSH
• fytonutrienty * MeSH