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 relationships (QSTAR) has been applied to the data on inhibition of Escherichia coli 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 individual derivatives was characterized by the equieffective concentrations causing the 50%-decrease in the specific growth rate in comparison with the untreated control. The QSTAR models satisfactorily describe toxicity of the studied compounds as a model-based non-linear function of hydrophobicity, the size of the substituents in the position 2, and the time of exposure. The dependence of the antibacterial activity on hydrophobicity at a fixed exposure time exhibits a broad maximum: the decrease for hydrophilic compounds is caused by their diminished ability for binding to the receptors and that for hydrophobic compounds is elicited by their lower concentrations in the aqueous phases and their slower inactivation. Inactivation is probably enzymatic because its rate depends on the size of the molecules. The size has a positive effect also on the binding to the receptor.