DETERMINATION OF THE LIPOPHILICITY PARAMETERS LOG P CALCD, RM0 AND LOG P TLC OF NEW ANTICANCER ACYLAMINOALKYL- AND SULFONYLAMINOALKYLAZAPHENOTHIAZINES BY COMPUTATIONAL METHODS AND REVERSED-PHASE THIN-LAYER CHROMATOGRAPHY

Abstract

The lipophilicity parameters of twenty-two new acylaminoalkyl- and sulfonylaminoalkyl-azaphenothiazines of two types (dipyridothiazines A1-A11 and diquinothiazines B1-B11 ) were determined theoretically using 11 computational methods and experimentally by reversed-phase thin-layer chromatography. The theoretical log P calcd values differed dramatically depending on the calculating programs. The experimental R M values were linearly dependent on the concentration of acetone in the mobile phase and extrapolated to 0% of acetone gave the lipophilicity parameter R M0, which was further transformed into the parameter log P TLC by use of a calibration curve. The parameter R M0 and specific hydrophobic surface area b were significantly intercorrelated showing congeneric classes of azaphenothiazines. The parameter R M0 was correlated with molecular descriptors (molar mass, molar volume and molar refractivity). Diquinothiazines B1-B11 were much more lipophilic than dipyridothiazines A1-A11 by 2.75–4.02 in logarithmic units. The theoretical log P calcd values were compared with experimental log P TLC values showing low prediction power of calculated programs. The determined parameters were discussed in the terms of the structure-lipophilicity relationships.