{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T01:57:02Z","timestamp":1783130222820,"version":"3.54.6"},"reference-count":55,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T00:00:00Z","timestamp":1523577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["AI090048"],"award-info":[{"award-number":["AI090048"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>As the threat associated with fungal infections continues to rise and the availability of antifungal drugs remains a concern, it becomes obvious that the need to bolster the antifungal armamentarium is urgent. Building from our previous findings of tobramycin (TOB) derivatives with antifungal activity, we further investigate the effects of various linkers on the biological activity of these aminoglycosides. Herein, we analyze how thioether, sulfone, triazole, amide, and ether functionalities affect the antifungal activity of alkylated TOB derivatives against 22 Candida, Cryptococcus, and Aspergillus species. We also evaluate their impact on the hemolysis of murine erythrocytes and the cytotoxicity against mammalian cell lines. While the triazole linker appears to confer optimal activity overall, all of the linkers incorporated into the TOB derivatives resulted in compounds that are very effective against the Cryptococcus neoformans species, with MIC values ranging from 0.48 to 3.9 \u03bcg\/mL.<\/jats:p>","DOI":"10.3390\/molecules23040899","type":"journal-article","created":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T14:38:14Z","timestamp":1523630294000},"page":"899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Differential Effects of Linkers on the Activity of Amphiphilic Tobramycin Antifungals"],"prefix":"10.3390","volume":"23","author":[{"given":"Marina","family":"Fosso","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjib","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nishad","family":"Thamban Chandrika","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Dennis","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7961-5555","authenticated-orcid":false,"given":"Sylvie","family":"Garneau-Tsodikova","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1002\/cbic.200900779","article-title":"The future of aminoglycosides: The end or renaissance?","volume":"11","author":"Houghton","year":"2010","journal-title":"ChemBioChem"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1039\/C5MD00344J","article-title":"Mechanisms of resistance to aminoglycoside antibiotics: Overview and perspectives","volume":"7","author":"Labby","year":"2016","journal-title":"MedChemComm"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1039\/C7CS00407A","article-title":"Comprehensive review of chemical strategies for the preparation of new aminoglycosides and their biological activities","volume":"47","year":"2018","journal-title":"Chem. 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