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

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). [GRAPHICS] .