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

Abstract

The lipophilicity parameters (logPcalcd, RM0 and logPTLC) 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 RM0 was determined on the RP-18 silica plates with acetone-aqueous TRIS buffer as mobile phase. The obtained parameter RM0 was further transformed into parameter logPTLC by use of the calibration curve. The theoretical logPcalcd values differed depending on the substituents and nature of calculating programs. Fluoroquinobenzothiazines turned out to be rather middling or highly lipophilic compounds. The parameter RM0 and specific hydrophobic surface area b were meaningly intercorrelated showing congeneric two classes of quinobenzothiazines. The calculated logPcalcd and experimental logPTLC 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).