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Review
. 2020 Jul 1;30(13):127218.
doi: 10.1016/j.bmcl.2020.127218. Epub 2020 Apr 25.

The relationship between the structure and toxicity of aminoglycoside antibiotics

Moriah Jospe-Kaufman  1 , Liza Siomin  2 , Micha Fridman  3
Affiliations
Review

The relationship between the structure and toxicity of aminoglycoside antibiotics

Moriah Jospe-Kaufman et al. Bioorg Med Chem Lett. .

Abstract

Aminoglycoside antibiotics, used to treat persistent gram-negative infections, tuberculosis, and life-threatening infections in neonates and patients with cystic fibrosis, can infer acute kidney injury and irreversible hearing loss. The full repertoire of cellular targets and processes leading to the toxicity of aminoglycosides is not fully resolved, making it challenging to devise rational directions to circumvent their adverse effects. As a result, there has been very limited effort to rationally address the issue of aminoglycoside-induced toxicity. Here we provide an overview of the reported effects of aminoglycosides on cells of the inner ear and on kidney tubular epithelial cells. We describe selected examples for structure-toxicity relationships established by evaluation of both natural and semisynthetic aminoglycosides. The various assays and models used to evaluate these antibiotics and recent progress in development of safer aminoglycoside antibiotics are discussed.

Keywords: Aminoglycosides; Antibiotics; Cochlear toxicity; Nephrotoxicity.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper

Figures

None
Graphical abstract
Fig. 1
Fig. 1
Treatment with AGs is frequently accompanied by nephrotoxic and ototoxic side-effects. (A) Schematic illustration of kidney proximal tubular cells. (B) Schematic illustration of the inner ear. (C) Images of organotypic cultures of mouse organ of corti cells cultured with or without 0.02 mM G-418 for 24 h and stained for actin.
Fig. 2
Fig. 2
Structures of the AGs streptomycin and its semisynthetic derivative dihydrostreptomycin and of paromomycin, neomycin B and gentamicin.
Fig. 3
Fig. 3
Structures of natural AGs and of semisynthetic analogs.
See this image and copyright information in PMC

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