STUDIES OF A POTENTIAL IN VITRO TEST FOR ESTIMATION OF TOXICITY OF AMINOGLYCOSIDE ANTIBIOTICS AND POLYAMINES

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The electrophoretic mobility of phosphatidyl inositol liposomes at pH 7.4, 25°C, was reduced by aminoglycoside antibiotics, neamine and several polyamines in general accordance with the number of amino-groups on each molecule. There was good agreement between the relative position of the tested compounds on the mobility-concentration graph and available information about their relative mammalian toxicities in vivo. The slope of the graph for netilmicin was distinctively flat; a comparatively flat dose-response curve for netilmicin has been reported also from in vivo studies of nephrotoxicity. Investigation of a homologous series of α, ω, straight chain diaminoalkanes revealed that hydrophobicity did not contribute significantly to the observed interaction in this system. L-Lysine showed the weakest effect amongst all compounds tested, supporting the view that the overall positive charge on the molecule was the major determinant of the observed effect. Further structure-activity work is required to confirm whether this 'in vitro' test is predictive of the toxicity of aminoglycoside antibiotics in man.