{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T12:29:02Z","timestamp":1790771342206,"version":"4.1.0"},"reference-count":41,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2015,8,1]],"date-time":"2015-08-01T00:00:00Z","timestamp":1438387200000},"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":[[2015,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            In this study, we investigated the\n            <jats:italic>in vitro<\/jats:italic>\n            antifungal activities, cytotoxicities, and membrane-disruptive actions of amphiphilic tobramycin (TOB) analogues. The antifungal activities were established by determination of MIC values and in time-kill studies. Cytotoxicity was evaluated in mammalian cell lines. The fungal membrane-disruptive action of these analogues was studied by using the membrane-impermeable dye propidium iodide. TOB analogues bearing a linear alkyl chain at their 6\u2033-position in a thioether linkage exhibited chain length-dependent antifungal activities. Analogues with C\n            <jats:sub>12<\/jats:sub>\n            and C\n            <jats:sub>14<\/jats:sub>\n            chains showed promising antifungal activities against tested fungal strains, with MIC values ranging from 1.95 to 62.5 mg\/liter and 1.95 to 7.8 mg\/liter, respectively. However, C\n            <jats:sub>4<\/jats:sub>\n            , C\n            <jats:sub>6<\/jats:sub>\n            , and C\n            <jats:sub>8<\/jats:sub>\n            TOB analogues and TOB itself exhibited little to no antifungal activity. Fifty percent inhibitory concentrations (IC\n            <jats:sub>50<\/jats:sub>\n            s) for the most potent TOB analogues (C\n            <jats:sub>12<\/jats:sub>\n            and C\n            <jats:sub>14<\/jats:sub>\n            ) against A549 and Beas 2B cells were 4- to 64-fold and 32- to 64-fold higher, respectively, than their antifungal MIC values against various fungi. Unlike conventional aminoglycoside antibiotics, TOB analogues with alkyl chain lengths of C\n            <jats:sub>12<\/jats:sub>\n            and C\n            <jats:sub>14<\/jats:sub>\n            appear to inhibit fungi by inducing apoptosis and disrupting the fungal membrane as a novel mechanism of action. Amphiphilic TOB analogues showed broad-spectrum antifungal activities with minimal mammalian cell cytotoxicity. This study provides novel lead compounds for the development of antifungal drugs.\n          <\/jats:p>","DOI":"10.1128\/aac.00229-15","type":"journal-article","created":{"date-parts":[[2015,6,2]],"date-time":"2015-06-02T13:55:09Z","timestamp":1433253309000},"page":"4861-4869","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":67,"title":["Amphiphilic Tobramycin Analogues as Antibacterial and Antifungal Agents"],"prefix":"10.1128","volume":"59","author":[{"given":"Sanjib K.","family":"Shrestha","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina Y.","family":"Fosso","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith D.","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie","family":"Garneau-Tsodikova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Kentucky, Lexington, Kentucky, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.9.4.499"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/20.6.1526"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.42.10.4419-4431.2004"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.274"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.47.8.2565-2571.2003"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2672.2005.02684.x"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200761"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2010.110"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0073843"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4MD00078A"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1039\/C4MD00163J"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1105379108"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00312-11"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200900584"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.10.119"},{"key":"e_1_3_2_17_2","volume-title":"CLSI document M07-A9","author":"Clinical and Laboratory Standards Institute","year":"2012","unstructured":"Clinical and Laboratory Standards Institute. 2012. 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