DETERMINATION OF THE LIPOPHILICITY PARAMETERS OF NEW ANTIPROLIFERATIVE 8-10-SUBSTITUTED QUINOBENZOTHIAZINES BY COMPUTATIONAL METHODS AND RP TLC

The lipophilicity parameters of fourteen new antiproliferative 8-10-substituted 6H-quinobenzothiazines were determined theoretically using 9 computational methods and experimentally by reversed-phase thin-layer chromatography on the RP-18 silica plates with acetone-aqueous TRIS buffer as the mobile phase. The experimental R (M) values were linearly dependent on the concentration of acetone in the mobile phase and extrapolated to 0% of acetone that produced the lipophilicity parameter R (M0). The parameter R (M0) and specific hydrophobic surface area b were significantly intercorrelated showing congeneric classes of quinobenzothiazines. The parameter R (M0) was correlated with molecular descriptors (molar mass, molar volume, and molar refractivity), predicted and tested biological activities, and was further transformed into parameter log P-TLC by use of the calibration curve. The theoretical log P (calcd) values differed depending on the calculating programs and were compared with experimental log P-TLC values showing different prediction powers of calculated programs. Tetracyclic 6H-quinobenzothiazine was as lipophilic as tricyclic 10H-phenothiazine. The determined parameters are discussed in the terms of the structure-lipophilicity relationships.