QUANTITATIVE STRUCTURE-TIME-ACTIVITY RELATIONSHIPS (QSTAR) - GROWTH-INHIBITION OF ESCHERICHIA-COLI BY NONIONIZABLE KOJIC ACID-DERIVATIVES

A semi-empirical model for quantitative structure-time-activity relati onships (QSTAR) has been applied to the data on inhibition of Escheric hia call in a batch culture in seven media of different acidity (pH 5. 6-8.0) by twenty one nonionizable derivatives of kojic acid (5-hydroxy -2-hydroxymethyl-4H-pyrane-4-one). The antibacterial potency of indivi dual derivatives was characterized by the equieffective concentrations causing the 50%-decrease in the specific growth rate in comparison wi th the untreated control. The QSTAR models satisfactorily describe tox icity of the studied compounds as a model-based non-linear function of hydrophobicity, the size of the substituents in the position 2, and t he time of exposure. The dependence of the antibacterial activity on h ydrophobicity at a fixed exposure time exhibits a broad maximum: the d ecrease for hydrophilic compounds is caused by their diminished abilit y for binding to the receptors and that for hydrophobic compounds is e licited by their lower concentrations in the aqueous phases and their slower inactivation. Inactivation is probably enzymatic because its ra te depends on the size of the molecules. The size has a positive effec t also on the binding to the receptor.