Correlation of HPLC Retention Data of Triazines with the Inhibition of DHFR from L1210 Cells: Development of New Chromatographic Adsorption Parameter in QSAR

Abstract

The use of chromatographic retention measurements for quantitative structure—activity relationships (QSAR) was investigated by the development of an adjusted logarithmic retention factor. Retention data of 15 triazine derivatives, which inhibit dihydrofolate reductase were measured by HPLC on octyl-silica and silica gel columns. From these data two parameters were calculated. First, the intercept of the plot of the logarithmic retention factor versus acetonitrile concentration was calculated from the reversed-phase retention measurements (log k'o) and, second, the difference between the logarithmic retention factor at high ammonium salt concentration and low ammonium salt concentration in the mobile phase was calculated from retention measurements on the silica gel column. The first parameter represents hydrophobic properties and the second parameter characterizes adsorption properties of the triazine derivatives. The results show a correlation between the two above mentioned parameters and the inhibition of L1210/71 cell growth.