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

Abstract

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.

Keywords:

• Congeneric classes
• correlation analysis
• lipophilicity
• phenothiazines
• quinobenzothiazines
• reversed-phase thin-layer chromatography