Computational Exploration of Bioactive Compounds from Curcuma xanthorrhiza Roxb. as Potential Antibacterial Agents against Antibiotic-Resistant Strains Targeting PBP۲X

The emergence of antibiotic-resistant bacteria poses a critical global health threat, complicating the treatment of common infections and severely limiting the availability of effective antibiotics. Curcuma xanthorrhiza Roxb., a medicinal plant with diverse pharmacological properties, is believed to exhibit significant antibacterial potential. This study aimed to identify potent antibacterial compounds from C. xanthorrhiza and to elucidate their mechanisms of action through computational approaches. Bioactive compounds from C. xanthorrhiza were screened for drug-likeness, toxicity, membrane permeability, and bioactivity. Protein target predictions were conducted based on prior research, focusing on bacterial penicillin-binding protein ۲X (PBP۲X), a key player in bacterial cell wall synthesis. Molecular docking was performed using AutoDock Vina integrated with PyRx ۸.۰, and molecular dynamics simulations were carried out with CABS-flex ۲.۰ to evaluate interaction stability. The study identified ۳,۴-dihydroxybisabola-۱,۱۰-diene and dehydro-۶-gingerdione as promising antibacterial candidates. These compounds met all screening criteria and demonstrated superior antibacterial potential against antibiotic-resistant bacteria compared to other bioactive molecules. Docking analysis revealed that both compounds bind effectively to the inhibitor sites of PBP۲X, while molecular dynamics simulations confirmed their stable interactions with the target, supported by favorable RMSF and binding energy values. In conclusion, ۳,۴-dihydroxybisabola-۱,۱۰-diene and dehydro-۶-gingerdione from C. xanthorrhiza emerge as potential antibacterial agents by targeting PBP۲X, offering a promising avenue for combating antibiotic-resistant bacterial infections.

کلیدواژه ها:

۳ ، ۴-dihydroxybisabola-۱ ، ۱۰-diene ، Dehydro-۶-gingerdione ، Antibacterial ، Zingiberaceae