{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T11:49:33Z","timestamp":1788954573713,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T00:00:00Z","timestamp":1737590400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["T4-AN-07"],"award-info":[{"award-number":["T4-AN-07"]}]},{"name":"Italian Ministry of Health","award":["ECS00000017"],"award-info":[{"award-number":["ECS00000017"]}]},{"name":"PNRR THE e Tuscany Health Ecosystem;","award":["T4-AN-07"],"award-info":[{"award-number":["T4-AN-07"]}]},{"name":"PNRR THE e Tuscany Health Ecosystem;","award":["ECS00000017"],"award-info":[{"award-number":["ECS00000017"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: The ability of bacteria to form biofilms makes them more tolerant to traditional antibiotics. Given the lack of new antibiotic development, drug repurposing offers a strategy for discovering new treatments. Auranofin (AF), a gold-based compound indicated for the treatment of rheumatoid arthritis, shows promising antibacterial activity. This study investigates the antimicrobial and antibiofilm activity of AF and its two derivatives in which the thiosugar ligand is replaced by acetylcysteine (AF-AcCys) or naproxen (AF-Napx), against Staphylococcus aureus and Staphylococcus epidermidis. Methods: AF was conjugated by transmetalation with either naproxen or acetylcysteine. Assessments of their stability in DMSO\/H2O and lipophilicity expressed as the LogP were performed. The antimicrobial activity of AF and its analogues were investigated by broth microdilution assay to determine the minimum inhibitory concentration (MIC) and versus biofilm to obtain the minimum bactericidal biofilm concentration (MBBC) and minimum biofilm eradication concentration (MBEC). Results: AF derivatives were found to be stable in a DMSO\/H2O mixture for 48 h. AF-Napx showed a LogP = 1.25 \u00b1 0.22, close to AF, while AF-AcCys had a LogP = \u22120.95. MIC values of S. aureus and S. epidermidis were ranging from 2 \u00b5M to 0.25 \u00b5M, and \u22640.12 \u00b5M, respectively. Both AF and AF-Napx maintained efficacy against biofilm-embedded S. aureus and S. epidermidis at non-cytotoxic concentrations, with AF-Napx demonstrating lower MBBC values for S. epidermidis. Conclusions: AF, and especially its naproxen conjugate, holds potential as a therapeutic agent for treating biofilm-associated infections caused by S. aureus and S. epidermidis, particularly in device-related infections where both infection and inflammation are present.<\/jats:p>","DOI":"10.3390\/antibiotics14020118","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T04:54:31Z","timestamp":1737608071000},"page":"118","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Antimicrobial and Antibiofilm Activity of Auranofin and Its Two Derivatives Bearing Naproxen and Acetylcysteine as Ligands Against Staphylococci"],"prefix":"10.3390","volume":"14","author":[{"given":"Caterina","family":"Ferretti","sequence":"first","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"},{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4857-9819","authenticated-orcid":false,"given":"Lorenzo","family":"Chiaverini","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noemi","family":"Poma","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Dalli","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5051-1584","authenticated-orcid":false,"given":"Riccardo","family":"Di Leo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"},{"name":"CNR IFC, Institute of Clinical Physiology, National Research Council of Italy CNR Research Area, 56124 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7036-1192","authenticated-orcid":false,"given":"Laura","family":"Rindi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8311-8172","authenticated-orcid":false,"given":"Alessandro","family":"Marrone","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Chieti-Pescara \u201cG. D\u2019Annunzio\u201d, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9700-5331","authenticated-orcid":false,"given":"Iogann","family":"Tolbatov","sequence":"additional","affiliation":[{"name":"Department of Chemical, Physical, Mathematical and Natural Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4193-7612","authenticated-orcid":false,"given":"Diego","family":"La Mendola","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5791-686X","authenticated-orcid":false,"given":"Arianna","family":"Tavanti","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-3637","authenticated-orcid":false,"given":"Tiziano","family":"Marzo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0688-034X","authenticated-orcid":false,"given":"Mariagrazia","family":"Di Luca","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e51034","DOI":"10.15252\/embr.202051034","article-title":"Antibiotic resistance and persistence\u2014Implications for human health and treatment perspectives","volume":"21","author":"Huemer","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_2","first-page":"277","article-title":"The antibiotic resistance crisis: Part 1: Causes and threats","volume":"40","author":"Ventola","year":"2015","journal-title":"P&T"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Oliva, A., Stefani, S., Venditti, M., and Di Domenico, E.G. 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