Lipophilicity estimation of anti-proliferative and anti-inflammatory 6-substituted 9-fluoroquino[3,2-b]benzo[1,4]thiazines

Abstract

The lipophilicity parameters (logP_calcd, R_M0 and logP_TLC) of 17 new anti-proliferative and anti-inflammatory tetracyclic 6-substituted 9-fluoroquinobenzothiazines were determined theoretically using computational methods and experimentally by reversed-phase thin-layer chromatography. The experimental parameter R_M0 was determined on the RP-18 silica plates with acetone-aqueous TRIS buffer as mobile phase. The obtained parameter R_M0 was further transformed into parameter logP_TLC by use of the calibration curve. The theoretical logP_calcd values differed depending on the substituents and nature of calculating programs. Fluoroquinobenzothiazines turned out to be rather middling or highly lipophilic compounds. The parameter R_M0 and specific hydrophobic surface area b were meaningly intercorrelated showing congeneric two classes of quinobenzothiazines. The calculated logP_calcd and experimental logP_TLC values were compared and intercorrelated to show different prediction power of the computational programs. The lipophilicity was correlated with molecular descriptors (molar mass, molar volume, and molar refractivity), biomolecular descriptors (HIA, PB, MDCK, Caco-2, and BBB) and in vitro tested biological activities (tumor necrosis factor alpha inhibition and antiproliferative activity).

Graphical Abstract

Keywords:

• Lipophilicity
• reversed-phase thin-layer chromatography
• congeneric classes
• correlation analysis
• quinobenzothiazines
• azaphenothiazines

Additional information

Funding

The work is supported by the Medical University of Silesia in Katowice, [grant KNW-1-072/K/8/O].