Synthesis, Antibacterial Evaluation, and Chemometric Profiling of a Vanilloid-Based Compounds Library Active Against Helicobacter pylori
Antibiotics, cilt.15, sa.8, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 15 Sayı: 8
- Basım Tarihi: 2026
- Doi Numarası: 10.3390/antibiotics15080729
- Dergi Adı: Antibiotics
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, EMBASE, Directory of Open Access Journals, Natural Science Collection (ProQuest), Biological Science Database (ProQuest)
- Anahtar Kelimeler: artificial neural networks, GES-1, Helicobacter pylori, hierarchical cluster analysis, MBC, MIC, molecular docking, time-killing, vanillin
- Sivas Cumhuriyet Üniversitesi Adresli: Evet
Özet
Background: Among natural products, vanillin (Van), a major component of Vanilla planifolia, exhibits multiple bioactivities, including antimicrobial effects. Methods: In this study, Van, its analogues o-vanillin (oVan), iso-vanillin (iVan), ethylvanillin (eVan), and a library of newly synthesized derivatives were evaluated against Helicobacter pylori strains with distinct antibiotic susceptibilities. Time-kill kinetics, antibacterial spectrum, and viability in a normal gastric cell line GES-1, were also assessed. Results: Van showed minimal or no activity (MIC and MBC > 128 µg/mL), whereas structural modifications markedly improved anti-H. pylori activity, with MIC values as low as 4 µg/mL. Compounds 16V, 20oV, and 29eV were among the most potent (MIC90 = 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 H. pylori urease suggested that several compounds, particularly 16V, may interact with the enzyme, providing preliminary support for a possible involvement of this target. Conclusions: Systematic modification of the vanilloid scaffold generated selective and relatively non-cytotoxic anti-H. pylori hit compounds and confirmed the value of natural metabolites in antibacterial drug discovery.