In vitro and in silico validation of the therapeutic potential of Tea tree (Melaleuca alternifolia) oil through GC/MS integrated profiling, and molecular dynamic simulation
摘要
The emerging prevalence of antimicrobial resistance and the complexity of chronic wounds demand the advancement of novel therapeutic agents with enhanced efficacy and safety. Tea Tree Oil (TTO), derived from Melaleuca alternifolia, has been well-known for its broad-spectrum antibacterial, antifungal, and antioxidant properties. This study investigates the biological potency of TTO against predominant wound pathogens through a comprehensive in vitro and in silico approach. TTO exhibited good antimicrobial activity against the tested microbial strains with zone of inhibition in the range of 10–17 mm diameter, except that of Pseudomonas aeruginosa. Antioxidant activity estimated through radical scavenging assay also exhibits an IC50 value of 95.41 µl/ml, supporting its role in reducing oxidative stress in infected wound regions. GC/MS analysis revealed the presence of key constituents such as limonene, α-terpinene, cineol, camphor, linalool, carvomenthenol, and terpineol. All compounds revealed through GC/MS analysis of TTO demonstrated favourable drug-likeliness and pharmacokinetic properties. Further, molecular docking studies were performed in silico on ADME-screened drug-like ligands against wound pathogen-specific protein targets. Notably, the compound 1,8-cineol showed the highest docking affinity with the Candida albicans target protein 1NMT, which is related the fungal existence and metabolism. MD simulation analysis, such as RMSD, Rg, RMSF, SASA, PCA, and FEL, confirmed the stability of the ligand with the target protein, elucidating the chemical composition and mechanism of action at a molecular level. This study fills a crucial research gap by demonstrating that TTO is a promising natural agent for the development of topical formulations for wound-infection control.