Molecular encapsulation of the protocatechuic and vanillic acid derivatives with β-cyclodextrin: Structural determination, antibacterial assessment, and molecular docking analysis

The phenolic chemical framework represents one of the most utilized structural motifs in the pursuit of innovative biologically active compounds. Particularly, the urgency for efficient antibacterial agents is still ongoing, especially due to rising bacterial resistance to common therapeutics. The physicochemical profile and efficiency of bioactive agents could be enhanced by their inclusion with cyclodextrins. In this study, the encapsulation of four protocatechuic and vanillic acid derivatives was performed in the reactions with β-cyclodextrin. The host-guest interactions and the formation of inclusion systems were confirmed by NMR, IR, and XRPD spectra. The Job's plot assay revealed the 1:1 stoichiometric ratio in the formed inclusion complexes, whereas the molecular docking analysis exposed the most favorable inclusion modes of guest molecules within the β-cyclodextrin cavity. The in vitro antibacterial investigations performed on selected G+ and G− bacteria revealed significantly enhanced activity of inclusion complexes in comparison to guest molecules. In general, the tested substances exhibited antibacterial activity with the MIC50 values determined in the range of 0.20–7.98 mM. Here, L. monocytogenes (G+) and E. coli (G−) strains were most sensitive to the treatment with guests and inclusion complexes. In several cases, the investigated compounds exerted comparable or higher activity than vancomycin. The present findings indicate that encapsulation of the selected phenolic compounds is favorable for improving their antibacterial profile, which could contribute to the endeavor for more efficient antibiotic therapy.