The Lipophilicity Parameters of New Antiproliferative 6,9-Disubstituted Quinobenzothiazines Determined by Computational Methods and RP TLC

The lipophilicity parameters (log P-calcd, R-M0, and log P-TLC) of 54 new antiproliferative 6,9-disubstituted quinobenzothiazines were determined theoretically using eight computational methods and experimentally by reversed-phase thin-layer chromatography on the RP-18 silica plates with acetone-aqueous tris(hydroxymethyl)aminomethane buffer as mobile phase. The theoretical log P-calcd values differed depending on the substituents and calculating programs. The experimental parameters R-M0 and b (specific hydrophobic surface area) were intercorrelated showing congeneric classes of quinobenzothiazines. The parameter R-M0 was further transformed into parameter log P-TLC by use of the calibration curve. Generally, tetracyclic quinobenzothiazines turned out to be rather highly lipophilic compounds. The comparison of the calculated log P-calcd and experimental log P-TLC values showed different prediction power of the computational programs. The determined parameters were discussed in the terms of the structure-lipophilicity relationships. The R-M0 values were correlated with molecular descriptors (molar mass, molar volume, and molar refractivity) and predicted and tested biological activities.