{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T17:17:12Z","timestamp":1785172632299,"version":"3.55.0"},"reference-count":77,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Italian Ministry of Education, Universities and Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>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 &gt; 128 \u00b5g\/mL), whereas structural modifications markedly improved anti-H. pylori activity, with MIC values as low as 4 \u00b5g\/mL. Compounds 16V, 20oV, and 29eV were among the most potent (MIC90 = 4\u201316 \u00b5g\/mL). Activity depended on both the vanilloid core and substituent type. The compounds were inactive against representative Gram-negative and Gram-positive bacteria (MIC &gt; 128 \u00b5g\/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.<\/jats:p>","DOI":"10.3390\/antibiotics15080729","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"729","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis, Antibacterial Evaluation, and Chemometric Profiling of a Vanilloid-Based Compounds Library Active Against Helicobacter pylori"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4870-7326","authenticated-orcid":false,"given":"Ilaria","family":"D\u2019Agostino","sequence":"first","affiliation":[{"name":"Department of Pharmacy, University of Pisa, via Bonanno 6, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-9894","authenticated-orcid":false,"given":"Strahinja","family":"Kova\u010devi\u0107","sequence":"additional","affiliation":[{"name":"Faculty of Technology Novi Sad, University of Novi Sad, Bulevar cara Lazara 1, 21000 Novi Sad, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-4364","authenticated-orcid":false,"given":"Moataz A.","family":"Shaldam","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4369-1772","authenticated-orcid":false,"given":"Alessandra","family":"Ammazzalorso","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5870-7509","authenticated-orcid":false,"given":"Cristina","family":"Campestre","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Guglielmi","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8703-3635","authenticated-orcid":false,"given":"Michele","family":"Coluccia","sequence":"additional","affiliation":[{"name":"Department of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Gilardoni","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7363-8801","authenticated-orcid":false,"given":"Okan","family":"Ayka\u00e7","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, 58000 Sivas, Turkey"},{"name":"Department of Pharmaceutical Chemistry, Institute of Health Sciences, Inonu University, 44000 Malatya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9290-938X","authenticated-orcid":false,"given":"\u0130rem","family":"Bozbey Merde","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Inonu University, 44000 Malatya, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0166-2164","authenticated-orcid":false,"given":"Francesca","family":"Sisto","sequence":"additional","affiliation":[{"name":"Department of Biomedical, Surgical and Dental Sciences, University of Milan, Via Pascal 36, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8698-9440","authenticated-orcid":false,"given":"Simone","family":"Carradori","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, \u201cG. d\u2019Annunzio\u201d University of Chieti-Pescara, via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"104580","DOI":"10.1016\/j.drudis.2025.104580","article-title":"Structural Biology of Plant-Derived Antibacterials: Opportunities for Rational Lead Optimization","volume":"31","author":"Patra","year":"2026","journal-title":"Drug Discov. 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