Correlation of Chemical Structure and Ototoxicity in the Ototoxic Drugs

Abstract

Tuberactinomycin (Tum) is one of the peptide antibiotics with pharmacological character similar to kanamycin. Thirteen derivatives of Tum were prepared by replacing the R1 branch to various amino acids. The degree of ototoxicity of these derivatives was evaluated in comparison with their chemical structure. The isolated posterior semicircular canal of the bull frog was used. The ampullary nerve action potential in response to mechanical endolymphatic flow was recorded in normal Ringer's solution and in solutions with Tum of 2.5 mg/ml or Tum of 5.0 mg/ml. The degree of ototoxicity was determined by the amount of decrease in the maximum spike count. The derivatives of Rim with R1 branch containing acidic or basic groups of amino acid showed greater ototoxicity than those containing aliphatic side chains.