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Open AccessArticle

Antifungal Activities of 4″,6″-Disubstituted Amphiphilic Kanamycins

Department of Chemistry and Biochemistry, Utah State University, 0300 Old Main Hill, Logan, UT 84322-0300, USA
Department of Biology, Utah State University, 5305 Old Main Hill, Logan, UT 84322-5305, USA
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Molecules 2019, 24(10), 1882;
Received: 16 April 2019 / Revised: 10 May 2019 / Accepted: 14 May 2019 / Published: 16 May 2019
(This article belongs to the Special Issue Recent Development on the New Applications of Aminoglycosides)
Amphiphilic kanamycins derived from the classic antibiotic kanamycin have attracted interest due to their novel bioactivities beyond inhibition of bacteria. In this study, the recently described 4″,6″-diaryl amphiphilic kanamycins reported as inhibitors of connexin were examined for their antifungal activities. Nearly all 4″,6″-diaryl amphiphilic kanamycins tested had antifungal activities comparable to those of 4″,6″-dialkyl amphiphilic kanamycins, reported previously against several fungal strains. The minimal growth inhibitory concentrations (MICs) correlated with the degree of amphiphilicity (cLogD) of the di-substituted amphiphilic kanamycins. Using the fluorogenic dyes, SYTOXTM Green and propidium iodide, the most active compounds at the corresponding MICs or at 2×MICs caused biphasic dye fluorescence increases over time with intact cells. Further lowering the concentrations to half MICs caused first-order dye fluorescence increases. Interestingly, 4×MIC or 8×MIC levels resulted in fluorescence suppression that did not correlate with the MIC and plasma membrane permeabilization. The results show that 4″,6″-diaryl amphiphilic kanamycins are antifungal and that amphiphilicity parameter cLogD is useful for the design of the most membrane-active versions. A cautionary limitation of fluorescence suppression was revealed when using fluorogenic dyes to measure cell-permeation mechanisms with these antifungals at high concentrations. Finally, 4″,6″-diaryl amphiphilic kanamycins elevate the production of cellular reactive oxygen species as other reported amphiphilic kanamycins. View Full-Text
Keywords: amphiphilic kanamycin; Cryptococcus neoformans; antifungal; kinetic membrane permeabilization; SYTOXTM green; propidium iodide amphiphilic kanamycin; Cryptococcus neoformans; antifungal; kinetic membrane permeabilization; SYTOXTM green; propidium iodide
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MDPI and ACS Style

Alfindee, M.N.; Subedi, Y.P.; Grilley, M.M.; Takemoto, J.Y.; Chang, C.-W.T. Antifungal Activities of 4″,6″-Disubstituted Amphiphilic Kanamycins. Molecules 2019, 24, 1882.

AMA Style

Alfindee MN, Subedi YP, Grilley MM, Takemoto JY, Chang C-WT. Antifungal Activities of 4″,6″-Disubstituted Amphiphilic Kanamycins. Molecules. 2019; 24(10):1882.

Chicago/Turabian Style

Alfindee, Madher N.; Subedi, Yagya P.; Grilley, Michelle M.; Takemoto, Jon Y.; Chang, Cheng-Wei T. 2019. "Antifungal Activities of 4″,6″-Disubstituted Amphiphilic Kanamycins" Molecules 24, no. 10: 1882.

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