Chemical Profiling and Structure-Based Virtual Screening of Ukrainian Propolis Reveals Polyphenolic Compounds with Potential Activity against New Delhi Metallo-β-Lactamase-1

The global escalation of bacterial resistance to β-lactam antibiotics, primarily driven by the production of β-lactamase enzymes, represents a critical threat to public health. This study explores the potential of Ukrainian steppe bee propolis as a natural source of inhibitors targeting New Delhi metallo-β-lactamase-1 (NDM-1). Using high-performance liquid chromatography coupled with tandem mass spectrometry (LC–MS/MS), we identified a complex mixture of polyphenolic compounds, including pinocembrin, galangin, chrysin, and caffeic acid esters. In silico drug-likeness assessments based on the Lipinski, Veber, and Egan criteria demonstrated that these propolis-derived compounds occupy a favorable physicochemical space characterized by moderate lipophilicity and low polar surface area, suggesting improved potential for oral bioavailability compared to many clinically used β-lactamase inhibitors. Molecular docking simulations performed against the NDM-1 crystal structure (PDB ID: 8I8F) revealed that several natural compounds exhibit binding affinities stronger than those of established inhibitors such as tazobactam and avibactam. Notably, pinocembrin (–7.419 kcal/mol) and galangin (–7.395 kcal/mol) emerged as lead candidates, demonstrating stable interactions within the enzyme’s catalytic cavity in proximity to the active-site Zn²⁺ ions. These findings highlight Ukrainian propolis as a rich reservoir of bioactive scaffolds that may serve as effective adjuncts in antimicrobial therapy to combat β-lactam resistance.