title: Studies of a potential in vitro test for estimation of toxicity of aminoglycoside antibiotics and polyamines.
abstract: The electrophoretic mobility of phosphatidyl inositol liposomes at pH 7.4, 25 degrees 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 alpha,omega 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.
mesh_terms: D000617:Aminoglycosides / Q000633:toxicity; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D004586:Electrophoresis; D007674:Kidney Diseases / Q000139:chemically induced; D008081:Liposomes / Q000032:analysis*; D009428:Netilmicin / Q000633:toxicity; D011073:Polyamines / Q000633:toxicity*; D013329:Structure-Activity Relationship
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D008081:Liposomes; D011073:Polyamines; D009428:Netilmicin