Antibiotics · Published 2026-07-27 · DOI 10.3390/antibiotics15080729
Ilaria D’Agostino, Strahinja Kovačević, Moataz A. Shaldam, Alessandra Ammazzalorso, Cristina Campestre, Paolo Guglielmi, Michele Coluccia, Anna Gilardoni, Okan Aykaç, İrem Bozbey Merde, Francesca Sisto, Simone Carradori
<b>Background:</b> Among natural products, vanillin (<b>Van</b>), a major component of <i>Vanilla planifolia</i>, exhibits multiple bioactivities, including antimicrobial effects. <b>Methods:</b> In this study, <b>Van</b>, its analogues <i>o</i>-vanillin (<b>oVan</b>), <i>iso</i>-vanillin (<b>iVan</b>), ethylvanillin (<b>eVan</b>), and a library of newly synthesized derivatives were evaluated against <i>Helicobacter pylori</i> strains with distinct antibiotic susceptibilities. Time-kill kinetics, antibacterial spectrum, and viability in a normal gastric cell line GES-1, were also assessed. <b>Results: Van</b> showed minimal or no activity (MIC and MBC > 128 µg/mL), whereas structural modifications markedly improved anti-<i>H. pylori</i> activity, with MIC values as low as 4 µg/mL. Compounds <b>16V</b>, <b>20oV,</b> and <b>29eV</b> were among the most potent (MIC<sub>90</sub> = 4–16 µg/mL). Activity depended on both the vanilloid core and substituent type. The compounds were inactive against representative Gram-negative and Gram-positive bacteria (MIC > 128 µg/mL). Selected compounds preserved viability in GES-1 cells. Hierarchical clustering, artificial neural clustering, and principal component analysis identified potency-related architectural motifs and strain-specific activity. Docking against <i>H. pylori</i> urease suggested that several compounds, particularly <b>16V</b>, may interact with the enzyme, providing preliminary support for a possible involvement of this target. <b>Conclusions:</b> Systematic modification of the vanilloid scaffold generated selective and relatively non-cytotoxic anti-<i>H. pylori</i> hit compounds and confirmed the value of natural metabolites in antibacterial drug discovery.
Abstract from DOAJ. Public domain (CC0 1.0).
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D’Agostino, I., Kovačević, S., Shaldam, M., et al. (2026). Synthesis, Antibacterial Evaluation, and Chemometric Profiling of a Vanilloid-Based Compounds Library Active Against Helicobacter pylori. Antibiotics. https://doi.org/10.3390/antibiotics15080729