DETERMINATION OF THE LIPOPHILICITY PARAMETERS LOG P_CALCD, R_M0 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.

Keywords:

• azaphenothiazines
• congeneric classes
• lipophilicity
• RP TLC
• structure-lipophilicity relationship

ACKNOWLEDGMENT

The work is supported by the Medical University of Silesia (grant KNW-1-008/10).

Notes

Note: b (slope), a (intercept), r (correlation coefficient), and s (standard errors) from the correlation: log P _calcd = bR _M0 + a.

Note: b (slope) and r (correlation coefficient) from the linear relationship R _M = R _M0 + bC.

This article is Part CXIX in the series of Azinyl Sulfides.