{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T11:56:39Z","timestamp":1781265399966,"version":"3.54.1"},"reference-count":34,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Recovery and Resilience Plan"},{"name":"European Union\u2014NextGenerationEU","award":["CN_00000033"],"award-info":[{"award-number":["CN_00000033"]}]},{"name":"Italian Ministry of University and Research","award":["CUP B73C22000790001"],"award-info":[{"award-number":["CUP B73C22000790001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Biofilm-related infections represent a major concern in clinical practice because of their poor responsiveness to standard antimicrobial treatments. Over the past decade, many efforts have been made to identify new compounds capable of inhibiting this particularly resistant form of bacterial life. Although several compounds have shown interesting anti-biofilm properties, none have reached the clinic. Methods: In the present work, we describe the synthesis and biological assessment as anti-biofilm agents, of a novel library of twenty-one imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines. Results: The newly synthesized compounds were in vitro evaluated for their ability to prevent biofilm formation and to eradicate established biofilms in Staphylococcus aureus ATCC 25923 and Pseudomonas aeruginosa ATCC 15442. Additionally, the most potent compounds, 9g and 9u, were in vivo assayed for their safety profile and the anti-infective effect in a Galleria mellonella model. Conclusions: Derivatives 9g, 9i, 9n, 9q and 9u proved to be potent inhibitors of S. aureus biofilm showing BIC50 values lower than 15 \u00b5g\/mL. Noteworthy, the in vivo results revealed the promising protective properties of compound 9u in the early stage of staphylococcal infection.<\/jats:p>","DOI":"10.3390\/antibiotics15060598","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T09:49:51Z","timestamp":1781257791000},"page":"598","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Imidazo[2,1-b][1,3,4]thiadiazol-2-yl]-1H-pyrrolo[2,3-b]pyridines as Inhibitors of Staphylococcus aureus Biofilm Formation"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2416-0474","authenticated-orcid":false,"given":"Domenico","family":"Schillaci","sequence":"first","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiana","family":"Plescia","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabio","family":"Scian\u00f2","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6950-1881","authenticated-orcid":false,"given":"Federica","family":"Parisi","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9439-0980","authenticated-orcid":false,"given":"Valentina","family":"Catania","sequence":"additional","affiliation":[{"name":"Department of Earth and Marine Sciences (DiSTeM), University of Palermo, Viale delle Scienze Ed. 16, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8857-4847","authenticated-orcid":false,"given":"Barbara","family":"Manachini","sequence":"additional","affiliation":[{"name":"Department of Agricultural, Food and Forest Sciences (SAAF), University of Palermo, Viale delle Scienze 13, 90128 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9965-3818","authenticated-orcid":false,"given":"Serena","family":"Indelicato","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6592-4373","authenticated-orcid":false,"given":"Tania","family":"Ciaglia","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via G. Paolo II 132, Fisciano, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Di Dio","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Salerno, Via G. Paolo II 132, Fisciano, 84084 Salerno, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4725-1881","authenticated-orcid":false,"given":"Stella","family":"Cascioferro","sequence":"additional","affiliation":[{"name":"Department of Biological, Chemical, and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Via Archirafi 32, 90123 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"ref_1","first-page":"277","article-title":"The Antibiotic Resistance Crisis","volume":"40","author":"Ventola","year":"2015","journal-title":"Pharm. 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