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Review
. 2022 Sep 23:13:1000199.
doi: 10.3389/fmicb.2022.1000199. eCollection 2022.

Amphiphilic aminoglycosides: Modifications that revive old natural product antibiotics

Jon Y Takemoto  1 , Guillermo A Altenberg  2 , Naveena Poudyal  3 , Yagya P Subedi  3 , Cheng-Wei T Chang  3
Affiliations
Review

Amphiphilic aminoglycosides: Modifications that revive old natural product antibiotics

Jon Y Takemoto et al. Front Microbiol. .

Abstract

Widely-used Streptomyces-derived antibacterial aminoglycosides have encountered challenges because of antibiotic resistance and toxicity. Today, they are largely relegated to medicinal topical applications. However, chemical modification to amphiphilic aminoglycosides can revive their efficacy against bacterial pathogens and expand their targets to other pathogenic microbes and disorders associated with hyperactive connexin hemichannels. For example, amphiphilic versions of neomycin and neamine are not subject to resistance and have expanded antibacterial spectra, and amphiphilic kanamycins are effective antifungals and have promising therapeutic uses as connexin hemichannel inhibitors. With further research and discoveries aimed at improved formulations and delivery, amphiphilic aminoglycosides may achieve new horizons in pharmacopeia and agriculture for Streptomyces aminoglycosides beyond just serving as topical antibacterials.

Keywords: amphiphilic aminoglycosides; antibiotic resistance; connexin; kanamycin; neamine; neomycin.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Structures of natural AGs.
FIGURE 2
FIGURE 2
Structures of semisynthetic aminoglycosides.
FIGURE 3
FIGURE 3
Structures of representative amphiphilic neomycins.
FIGURE 4
FIGURE 4
Synthesis of amphiphilic neamine.
FIGURE 5
FIGURE 5
Synthesis of AKs.
FIGURE 6
FIGURE 6
Synthesis of amphiphilic tobramycin.
FIGURE 7
FIGURE 7
Structures of FG08 and K20.
FIGURE 8
FIGURE 8
One-step synthesis of AKs 11a and 11b.
FIGURE 9
FIGURE 9
Amphiphilic kanamycin as connexin inhibitor.
See this image and copyright information in PMC

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