| Abstract: | Forty-five aminoglycoside antibiotics and related compounds were compared for their ability to induce the accumulation of dihydrostreptomycin in Escherichia coli K12. The common aminoglycosides and a streptothricin antibiotic all induced enhanced uptake within a relatively narrow concentration range. These concentrations were lethal to the bacteria. Comparison of aminoacyl derivatives of tobramycin and apramycin, the latter synthesized utilizing transition-metal cations to selectively control the site of substitution, revealed that 1-N-aminoacyl modifications resulted in an increased ability to induce enhanced uptake. 2'-N-Aminoacyl modifications were also effective at inducing enhanced uptake, albeit without noticeable improvement over parent. The findings from this structure-activity comparison support the proposition that aminoglycosides share a common critical target (most likely the ribosome), which, when acted upon, results in both drug accumulation and killing. |
