The relationship between the structure and toxicity of aminoglycoside antibiotics

[Display omitted] 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 proce...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2020-07, Vol.30 (13), p.127218-127218, Article 127218
Main Authors: Jospe-Kaufman, Moriah, Siomin, Liza, Fridman, Micha
Format: Article
Language:English
Subjects:
Aminoglycosides
Antibiotics
Cochlear toxicity
Nephrotoxicity
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Summary:[Display omitted] 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.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2020.127218