Evaluation of the lipophilicity of new anticancer 1,2,3-triazole-dipyridothiazine hybrids using RP TLC and different computational methods

Abstract

Two new anticancer-active 1,2,3-triazole-dipyridothiazine hybrids were evaluated for their lipophilicity using thin-layer chromatography (TLC) and computational methods. The experimental lipophilicity was evaluated with mobile phases (mixtures of TRIS buffer and acetone), exploiting a linear correlation between the retention parameter (RM) and the volume of acetone. The relative lipophilicity parameter (RM0) was obtained by extrapolation to 0% acetone concentration. This parameter was intercorrelated with a specific hydrophobic surface area (b) revealing two congeneric subgroups: hybrids of 1,2,3-triazole-2,7-diazaphenothiazines and 1,2,3-triazole-3,6-diazaphenothiazines. The parameter RM0 was converted into the absolute lipophilicity parameter logPTLC using a calibration curve prepared on the basis of compounds of known logP values. Triazole-dipyridothiazine hybrids turned out to be medium lipophilic with logPTLC values of 1.232-2.979. The chromatographically established parameter logPTLC was compared to the calculated lipophilic parameter logPcalcd obtained with various algorithms. The lipophilicity was correlated with molecular descriptors and ADME properties. The new triazole-dipyridothiazine hybrids followed Lipinski's rule of five. The lipophilicity of these hybrids was dependent on the substituents attached to the triazole ring and the location of the azine nitrogen atoms.