Medicinal Plant Power Against Superbugs: In-Silico Screening of Phytochemicals Targeting β-Lactamase-Mediated Antibiotic Resistance

Abstract

Background: Antibiotic resistance represents a major global public health threat, with multidrug-resistant bacterial strains increasingly described as “silent killers.” The rapid emergence of resistance has significantly reduced the effectiveness of conventional antibiotics, creating an urgent need for alternative or adjunct therapeutic strategies. Herbal medicines have been used for centuries, and according to the World Health Organization, approximately 70–80% of the global population relies on plant-based remedies for primary healthcare. Phytochemicals derived from medicinal plants possess diverse bioactive properties and have demonstrated promising antibacterial potential against resistant pathogens.

Methodology: In this study, an in silico screening approach was employed to evaluate the antibacterial potential of phytochemicals derived from Allium cepa, Acacia nilotica, and Azadirachta indica. Molecular docking was performed against three clinically relevant β-lactamase enzymes: AmpC (PDB ID: 1FSW) from Escherichia coli, OXA-48 (PDB ID: 7AUX) from Klebsiella pneumoniae, and VIM-2 (PDB ID: 5NI0) from Pseudomonas aeruginosa. These enzymes were selected due to their central role in conferring resistance to broad-spectrum β-lactam antibiotics. Ciprofloxacin, ampicillin, and cephalosporin were used as reference drugs for comparative binding analysis. Drug-likeness, physicochemical properties, and pharmacokinetic profiles of the top-ranked phytochemicals were further evaluated using Swiss ADME, and a heat map was generated to visualize their overall performance.

Results: Kaempferol and quercetin from Allium cepa exhibited strong binding affinities against the targeted β-lactamases. Phytochemicals such as apigenin, gallocatechin, and cyanidanol from Acacia nilotica, and caryophyllin from Azadirachta indica, demonstrated higher or comparable binding energies relative to standard antibiotics. Additionally, azadirachtol and acetylnimbandiol showed activity against multiple β-lactamases, indicating broad-spectrum potential.

Conclusion: The findings suggest that selected phytochemicals, including kaempferol, quercetin, cyanidanol, and caryophyllin, hold promise as lead compounds for the development of novel antibacterial agents or antibiotic adjuvants. These compounds may enhance the efficacy of existing antibiotics and help combat resistant bacterial infections. Although the in silico results are encouraging, further in vitro and in vivo studies are essential to validate their therapeutic potential.