Lipophilicity estimation of anti-proliferative and anti-inflammatory 6-substituted 9-fluoroquino[3, 2-b]benzo[1, 4]thiazines. Issue 17 (8th November 2019)

• Record Type: Journal Article
• Authors: Jeleń, Małgorzata; Pluta, Krystian; Morak-Młodawska, Beata
• Is Part Of: Journal of liquid chromatography & related technologies. Volume 42:Issue 17/18(2019)
• Page Start: 563
• Page End: 569
• Publication Date: 2019-11-08
• Subjects: Lipophilicity -- reversed-phase thin-layer chromatography -- congeneric classes -- correlation analysis -- quinobenzothiazines -- azaphenothiazines; Liquid chromatography -- Periodicals; Chromatographic analysis -- Periodicals; Separation (Technology) -- Periodicals; Biotechnology -- Periodicals; Chromatography, Liquid -- Periodicals; 543.8405
• DOI: 10.1080/10826076.2019.1636389
• Languages: English
• ISSNs: 1082-6076

Abstract

Abstract: The lipophilicity parameters (log P calcd, R M0 and log P 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 log P TLC by use of the calibration curve. The theoretical log P 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 log P calcd and experimental log P 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: