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Molecules 2018, 23(4), 899; https://doi.org/10.3390/molecules23040899

Differential Effects of Linkers on the Activity of Amphiphilic Tobramycin Antifungals

Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, USA
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Received: 2 April 2018 / Revised: 9 April 2018 / Accepted: 9 April 2018 / Published: 13 April 2018
(This article belongs to the Special Issue Recent Development on the New Applications of Aminoglycosides)
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Abstract

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 μg/mL. View Full-Text
Keywords: aminoglycosides; Aspergillus; Candida; Cryptococcus; cytotoxicity; hemolysis aminoglycosides; Aspergillus; Candida; Cryptococcus; cytotoxicity; hemolysis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

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Fosso, M.Y.; Shrestha, S.K.; Thamban Chandrika, N.; Dennis, E.K.; Green, K.D.; Garneau-Tsodikova, S. Differential Effects of Linkers on the Activity of Amphiphilic Tobramycin Antifungals. Molecules 2018, 23, 899.

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