Frontiers in pharmacology · 2026
In silico evaluation of potential penicillin-binding protein 2 (PBP2) inhibitors from Borassus flabellifer haustorium against cephalosporin-resistant Neisseria gonorrhoeae.
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Rajasekaran Udhaya, Sridharan T B
Аннотация
BACKGROUND: The emergence of cephalosporin-resistant Neisseria gonorrhoeae strains, encoding altered Penicillin-Binding Protein 2 (PBP2), has become a major global public health concern. The increasing prevalence of antimicrobial resistance necessitates the development of novel antimicrobial agents. In the present study, phytocompounds derived from the haustorium of Borassus flabellifer L. were investigated as potential inhibitors of PBP2 using an integrated in silico approach.
METHODOLOGY: Phytochemical profiling of the methanol, ethyl acetate and hexane extracts of white spongy palmyra haustorium was performed using GC-MS and the identified compounds were subsequently evaluated for molecular docking, ADMET analysis and molecular dynamics simulation.
RESULTS: A total of 69 compounds were identified and subjected to molecular docking against the transpeptidase domain of PBP2. The docking analysis revealed predicted binding affinities, ranging from -4.5 to -9.7 kcal/mol. The top ten compounds were subsequently evaluated for their ADMET and drug-likeness properties. Among these, 5-(4-nitrophenyl)-1,3,4-oxadiazol-2(5H)-one and 1,2,4-triazol-3-amine, 5-(1,3,5-trimethyl-4-pyrazolyl)amino, demonstrated comparatively favourable pharmacokinetic properties and balanced predicted ADMET profile. Furthermore, the stability of the complexes was assessed for a time period of 100 ns using molecular dynamics simulation. RMSD, RMSF, Rg, SASA, and hydrogen bonds were examined to evaluate protein-ligand interactions throughout the time frame. Principal component analysis and free energy landscape studies further supported ligand-induced stabilization of the PBP2 structure. MM-PBSA revealed favourable interaction energies of -19.11 ± 2.29 kJ/mol and -11.16 ± 2.34 kJ/mol for the two selected compounds, respectively. Among them, 5-(4-nitrophenyl)-1,3,4-oxadiazol-2(5H)-one demonstrated comparatively greater binding stability and thermodynamic favourability.
CONCLUSION: These findings suggest that 5-(4-nitrophenyl)-1,3,4-oxadiazol-2(5H)-one could serve as a promising lead molecule for the development of new therapeutics against drug-resistant gonococcal infections and necessitate further experimental validation.
METHODOLOGY: Phytochemical profiling of the methanol, ethyl acetate and hexane extracts of white spongy palmyra haustorium was performed using GC-MS and the identified compounds were subsequently evaluated for molecular docking, ADMET analysis and molecular dynamics simulation.
RESULTS: A total of 69 compounds were identified and subjected to molecular docking against the transpeptidase domain of PBP2. The docking analysis revealed predicted binding affinities, ranging from -4.5 to -9.7 kcal/mol. The top ten compounds were subsequently evaluated for their ADMET and drug-likeness properties. Among these, 5-(4-nitrophenyl)-1,3,4-oxadiazol-2(5H)-one and 1,2,4-triazol-3-amine, 5-(1,3,5-trimethyl-4-pyrazolyl)amino, demonstrated comparatively favourable pharmacokinetic properties and balanced predicted ADMET profile. Furthermore, the stability of the complexes was assessed for a time period of 100 ns using molecular dynamics simulation. RMSD, RMSF, Rg, SASA, and hydrogen bonds were examined to evaluate protein-ligand interactions throughout the time frame. Principal component analysis and free energy landscape studies further supported ligand-induced stabilization of the PBP2 structure. MM-PBSA revealed favourable interaction energies of -19.11 ± 2.29 kJ/mol and -11.16 ± 2.34 kJ/mol for the two selected compounds, respectively. Among them, 5-(4-nitrophenyl)-1,3,4-oxadiazol-2(5H)-one demonstrated comparatively greater binding stability and thermodynamic favourability.
CONCLUSION: These findings suggest that 5-(4-nitrophenyl)-1,3,4-oxadiazol-2(5H)-one could serve as a promising lead molecule for the development of new therapeutics against drug-resistant gonococcal infections and necessitate further experimental validation.