New approach for estimation of the biological activity of antimycotic substances

Reversed-phase, high-performance, thin-layer chromatographic data have been used to determine physicochemical parameters (retention factors, log k(w), and hydrophobicity, A(12)) describing the structural properties and phase affinity of 2,4-dihydroxythiobenzanilides. The retention factors (log k(w)) in pure water were determined by linear extrapolation from the experimenta l relationship between log k and the concentration of organic modifier in t he mobile phase. Special attention was paid to the chromatographic hydropho bicity, A(12), which is an expression of intermolecular interactions betwee n a solute and a two-phase liquid system. A(12) was derived from a thermody namic equation which assumes mixed adsorption and partition in the formatio n of the stationary phase, and a partition mechanism of solute distribution between the mobile and stationary phases. The parameters obtained were further used to estimate the hydrophobic chara cter and biological activity of the compounds examined. The results suggest ed that A(12) can be used as an indicator of the dependence of hydrophobici ty on phase affinity and substituent location. The good parabolic relations hip between antifungal activity and A(12) values for the 2,4-dihydroxythiob enzanilides examined enabled the proposal that A(12) can be used as a new p hysicochemical property in quantitative structure-activity relationship stu dies to predict biological activity.