Quantitative Structure-Activity Relationships of O-Acyl Derivatives of Leucomycin for Antimicrobial and Ribosome-Binding Activities

Abstract

Quantitative structure-activity relationships analyses of O-acylleucomycins for antimicrobial and ribosome-binding activities were carried out based on partition coefficient values. The analyses indicate that the antimicrobial activity against gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus and Micrococcus luteus) and the ribosome-binding activity are parabolically related to the hydrophobic character, and that the local hydrophobicity of the 3"-O-acyl group which is attached to the tertiary hydroxyl function is especially significant for the antimicrobial action. The correlation of antibacterial activity against gram-positive bacteria with ribosome-binding activity is also significant, but that in the case of gram-negative Escherichia coli is very poor. This discrepancy is considered to arise because the antimicrobial activity depends strongly on the ability of the drugs to permeate through the outer membranes (gram-positive bacteria do not have such membranes).