{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T08:11:00Z","timestamp":1790928660190,"version":"4.1.0"},"reference-count":145,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background. Positively charged quaternary phosphonium salts (QPSs) represent new potent weapons to selectively counteract critical superbugs, regardless of their profile of resistance, acting as membrane disruptors. QPSs 1, 3 and 4, and not cationic phosphine 2, recently synthesized, characterized and evaluated for anticancer and cytotoxic effects, were morphologically and microbiologically evaluated. Methods. DLS analysis, minimum inhibitory concentrations (MICs) measurements, time-kill experiments and tests to evaluate biofilm (BF) formation inhibition, on Gram-positive and Gram-negative clinical superbugs, were carried out. Results and Discussion. All compounds demonstrated positive \u03b6-p = +4.2\u2013+38.1 mV, while 2, 3 and 4 showed nanovesicles of 140, 157, and 605 nm, in water solution. Interesting microbiologic results were obtained for compound 1. Despite not being active against Gram-negative MDR isolates, 1 displayed MICs = 16\u201332 \u00b5g\/mL and 16\u201364 \u00b5g\/mL against methicillin-susceptible (MSSA) Staphylococcus aureus ATCC 29213, methicillin-resistant S. aureus (MRSA) and S. epidermidis (MRSE) respectively, while MICs = 32\u201364 \u00b5g\/mL were observed against teicoplanin- and vancomycin-resistant (VRE) Enterococcus faecalis and E. faecium, thus overturning MICs previously reported for 1. Novel time-kill experiments established the bactericidal effects of 1 against MRSA within 11 h, without no regrowth in the subsequent 24 h. Further, 1 inhibits up to 100% BF formation by the strongest BF-producers, S. epidermidis and S. aureus isolates, of our collection. Conclusions. All these antibacterial properties and low cytotoxicity on both fibroblasts (3T3) and human keratinocytes (HaCaT) cells make 1 appear as a potential new weapon to treat infections no longer affordable with current antibiotics; it is also thinkable for future use in vivo experiments and clinical development.<\/jats:p>","DOI":"10.3390\/ph19060829","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T08:16:08Z","timestamp":1779783368000},"page":"829","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Non-Cytotoxic Benzyl Triphenyl Phosphonium Bromide Is Bactericidal on MRSA and Fully Inhibits Biofilm Formation by MRSA and MRSE"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4630-4371","authenticated-orcid":false,"given":"Silvana","family":"Alfei","sequence":"first","affiliation":[{"name":"Department of Pharmacy (DIFAR), University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Piatti","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9868-6199","authenticated-orcid":false,"given":"Guendalina","family":"Zuccari","sequence":"additional","affiliation":[{"name":"Department of Pharmacy (DIFAR), University of Genoa, Viale Cembrano, 4, 16148 Genoa, Italy"},{"name":"Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caterina","family":"Reggio","sequence":"additional","affiliation":[{"name":"Laboratory of Experimental Therapies in Oncology, IRCCS Istituto Giannina Gaslini, Via G. Gaslini 5, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Schito","sequence":"additional","affiliation":[{"name":"Department of Surgical Sciences and Integrated Diagnostics (DISC), University of Genoa, Viale Benedetto XV, 6, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1016\/S1473-3099(12)70064-6","article-title":"Poor-Quality Antimalarial Drugs in Southeast Asia and Sub-Saharan Africa","volume":"12","author":"Nayyar","year":"2012","journal-title":"Lancet Infect. 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