In silico exploration of flavonoids against bacterial TEM-1 beta-lactamase

Abstract

The increasing prevalence of antibiotic resistance is a major public health concern worldwide, and the discovery of new antibacterial agents is urgently needed. Flavonoids are a diverse group of natural compounds that have been shown to possess antibacterial activity against a range of bacterial strains, including antibiotic-resistant strains. In this study, we used molecular docking to investigate the potential of flavonoids as inhibitors of TEM-1 beta-lactamase, which is a common enzyme responsible for resistance to beta-lactam antibiotics. We screened a library of flavonoids against the crystal structure of TEM-1 beta-lactamase (PDB: 1FQG) using the AutoDockVina software. Among the screened flavonoids, ZINC000013860547 showed the highest negative binding affinity (-9 kcal/mol) to the active site of TEM-1 beta-lactamase. We also analyzed the binding modes of ZINC000013860547 and found that it forms several hydrogen bonds and hydrophobic interactions with key residues in the active site of TEM-1 beta-lactamase. Our results suggest that ZINC000013860547 has the potential to be developed as a novel inhibitor of TEM-1 beta-lactamase after optimization, which may help to overcome beta-lactam resistance in bacterial infections. Further experimental studies are needed to validate the inhibitory activity of ZINC000013860547 against TEM-1 beta-lactamase and its potential as a therapeutic agent for antibiotic-resistant bacterial infections.