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Abstract

The cytotoxicity of four aminoglycoside antibiotics was studied by estimation of the dose-effect relationship using a panel cellular biotest system including cell cultures for test objects. The cultures represented 4 differentiation types: normal human fibroblasts and myoblasts, human or Syrian hamster hepatoma cells, and mouse/mouse hybridoma cells. It was found that three widely used antibiotics gentamicin, kanamycin, and neomycin exhibit similar, but not identical cytotoxicity parameters and differ distinctly from geneticin. Hence, the proposed panel biotest system helps to quantitatively evaluate and differentiate the effects of bioactive substances with similar chemical structure.

Increased Selectivity toward Cytoplasmic versus Mitochondrial Ribosome Confers Improved Efficiency of Synthetic Aminoglycosides in Fixing Damaged Genes: A Strategy for Treatment of Genetic Diseases Caused by Nonsense Mutations

“…All the tested compounds exhibited lower toxicity than that of gentamicin. Among all aminoglycosides tested, the aminoglycoside antibiotic, G418, which is known as one of the most cytotoxic aminoglycoside 11 , exhibited the lowest LC 50 value (1.3 mM). Very similar trend to that in HEK-293 cells (Table 1) was observed when such comparative cell toxicity was determined in human foreskin fibroblasts (HFF) cells (Table S1 in Supporting Information).…”

“…9, 10 G418 is however very cytotoxic to mammalian cells. 11 It has not been clear whether its high cytotoxicity is due to higher specificity to the mammalian ribosome or to some other feature. 12 Although the mitochondrial protein synthesis machinery is very similar to the prokaryotic machinery and the AGs-induced cytotoxicity may, at least in part, be connected to drug-mediated dysfunction of the mitochondrial ribosome, 13 the direct impact of synthetic AGs to the human mitochondrial ribosome has not yet been studied into details.…”

Translational Read-Through of a Nonsense Mutation Causing Bartter Syndrome

“…The chemical composition of aminoglycoside may influence on the efficiency of read-through and specific side effects (16, 23). For example, it is known that G418 may elicit specific side effects, such as vagina and oral mucosa ulceration in dogs (26). To improve termination-suppression activity and to lower the toxicity, several newer drugs have recently been identified (16, 27).…”

Chemo‐enzymatic Synthesis of Pseudo‐trisaccharide Aminoglycoside Antibiotics with Enhanced Nonsense Read‐through Inducer Activity

“…In other words, even though some studies using different cell lines have indicated amikacin and paromomycin as alternatives to gentamicin with respect to the NRI activity, data from clinical trials pertaining to the NRI activity of amikacin and paromomycin are still lacking. [18,19] Until recently, the majority of research studies investigating the NRI activity of compounds for the treatment of genetic disorders relied solely on commercially available AGs, and there have been almost no attempts to optimize NRI activity by modifying or reconstructing the chemical structures of AGs. [20] The research group in Israel and coworkers employed both chemical-and chemoenzymatic-techniques to synthesize various novel aminoglycoside derivatives or analogs.…”