{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T05:50:10Z","timestamp":1774936210954,"version":"3.50.1"},"reference-count":35,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            We present a novel family of small-molecule urinary bladder exfoliants that are expected to be of great value in preclinical studies of urologic conditions and have improved potential for translation compared with prior agents. There is broad urologic interest in the therapeutic potential of such exfoliating agents. The primary agent used in preclinical models, the cationic peptide protamine sulfate (PS), has limited translational potential due to concerns including systemic adverse reactions and bladder tissue injury. Intravesical application of a safe, systemically nontoxic exfoliant would have potential utility in the eradication of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Escherichia coli<\/jats:named-content>\n            and other uropathogens that reside in the bladder epithelium following cystitis, as well as in chronic bladder pain and bladder cancer. Here, we introduce a family of imidazolium salts with potent and focused exfoliating activity on the bladder epithelium. Synthesis and purification were straightforward and scalable, and the compounds exhibited prolonged stability in lyophilized form. Most members of the compound family were cytotoxic to cultured uroepithelial cells, with &gt;10-fold differences in potency across the series. Upon topical (intravesical) administration of selected compounds to the murine bladder, complete epithelial exfoliation was achieved with physiologically relevant imidazolium concentrations and brief contact times. The exfoliative activity of these compounds was markedly improved in comparison to PS, as assessed by microscopy, immunofluorescence, and immunoblotting for uroplakins. Bladder uroepithelium regenerated within days to yield a histologically normal appearance, and no toxicity was observed. Finally, the chemical scaffold offers an opportunity for inclusion of antimicrobials or conjugation with chemotherapeutic or other moieties.\n          <\/jats:p>","DOI":"10.1128\/aac.00881-15","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T02:44:58Z","timestamp":1435632298000},"page":"5494-5502","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Imidazolium Salts as Small-Molecule Urinary Bladder Exfoliants in a Murine Model"],"prefix":"10.1128","volume":"59","author":[{"given":"Patrick O.","family":"Wagers","sequence":"first","affiliation":[{"name":"Department of Chemistry and Center for Silver Therapeutics Research, University of Akron, Akron, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin M.","family":"Tiemann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerri L.","family":"Shelton","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Silver Therapeutics Research, University of Akron, Akron, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"William G.","family":"Kofron","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Silver Therapeutics Research, University of Akron, Akron, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Panzner","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Silver Therapeutics Research, University of Akron, Akron, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen L.","family":"Wooley","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Department of Chemical Engineering, and Department of Materials Science and Engineering, Texas A&amp;M University, College Station, Texas, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wiley J.","family":"Youngs","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Center for Silver Therapeutics Research, University of Akron, Akron, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9848-0975","authenticated-orcid":false,"given":"David A.","family":"Hunstad","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Washington University, St. Louis, Missouri, USA"},{"name":"Department of Molecular Microbiology, Washington University, St. Louis, Missouri, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00357068"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrurol.2010.190"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2002.5442"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.18.9630"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1084550"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2013.01.005"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.282.5393.1494"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040329"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134258"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0602136103"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.04.005"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00014-10"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.69.7.4572-4579.2001"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.70.12.7042-7049.2002"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093327"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0079-6468(08)70024-9"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/clc.4960070305"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(78)90232-4"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2008.00274.x"},{"key":"e_1_3_3_21_2","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1016\/S0140-6736(82)92362-5","article-title":"Protamine as a cause of generalised allergic reactions to NPH insulin","author":"Sanchez MB","year":"1982","unstructured":"Sanchez MB, Paolillo M, Chacon RS, Camejo M. 1982. 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