Investigations of Interactions of Chlormezanone Racemate and Its Enantiomers on Human Keratinocytes and Human Leucoytes in vitro

Abstract

Chlormezanone is a centrally acting muscle relaxant introduced in human therapy as a racemic substance. The following investigation was performed in order to investigate whether the racemate and both enantiomers differ in their potential cytotoxicty in vitro. We investigated antiproliferative effects and cytotoxicity (PicoGreen and ATP assay) for human HaCaT keratinocytes, production of oxygen radicals (ROS) by human interleukin-3-stimulated leukocytes (Lucigenin assay) and production of sulfoleukotrienes (Cellular Antigen Stimulation Test – CAST) by human leukocytes. In the dosage range of 0.001 to 0.1 mg/ ml chlormezanone, no antiproliferative effects were measured with the racemate and both enantiomers. At 1.0 mg/ml, a decrease of proliferative activity was seen after 48 h incubation time of about 50% for the enantiomers and of about 80% for the racemate (PicoGreen) and 50% (enantiomers) or 21% (racemate) in the ATP assay, respectively. ROS production was significantly inhibited at concentrations ≤0.01 mg/ ml by the racemate and the (+)-enantiomer, whereas the (–)-enantiomer was less effective. There was no stimulation of sulfidoleukotrienes in human leukocytes by chlormezanone. Present data argue for absence of significant cytotoxicity against human HaCaT keratinocytes and a dose-dependent suppression of ROS production by human leukocytes that is not uniform among the racemate and its enantiomers.

Carbene-Catalyzed Enantioselective Addition of Thioamides to Bromoenals for Access to Thiazinone Heterocycles

“…2 The thiazinone-containing chlormezanone is a commercial drug used as an anxiolytic and a muscle relaxant. 3 The BTZ043 is used to kill Mycobacterium tuberculosis. 4 Many methods have been developed to prepare these thiazines and their derivatives, mostly as achiral molecules or in racemic forms.…”

Efficient synthesis of N-substituted 1,3-thiazin-2-ones containing sulfonamide

“…The 1 H NMR spectra were recorded on a Bruker 400 MHz spectrometer using CDCl3 or DMSO-d6 as a solvent and tetramethylsilane (TMS) as internal reference. 13 C NMR and Dept 135 spectra were recorded on on a Bruker 100 MHz spectrometer using DMSO-d6 as a solvent and tetramethylsilane (TMS) as internal reference. Coupling constants (J values) are given in Hertz (Hz).…”

“…White solid (259.0 mg, 74%). Mp 85-86 °C; 1 H NMR (DMSO-d6) δ 8.48 (bs, 1H, NH), 6.29 (s, 1H, Ar-H), 7.05 (m, 3H, Ar-H), 3.58 (t, J 6.5 Hz, 2H,CH2N), 2.63 (t, J 6.5 Hz, 2H, CH2S), 1.86 (m, 2H, CH2); 13 C NMR (DMSO-d6) δ 169. 8, 143.7, 130.6, 123.2, 121.7, 120.3, 117.1, 44.7, 33.7, 27.4…”

“…12 The thiazin-4-one-containing chlormezanone is a commercial drug used as an anxiolytic and a muscle relaxant. 13 The sulfonamide group, moreover, is considered as a pharmacophore (that part of a molecular structure responsible for recognition and interaction with biological receptors), which is present in many biologically active molecules, particularly antimicrobial agents. 14 It was shown that sulfonamide moieties can enhance largely the activity of antibacterial agents, especially against both Gram-positive and Gram-negative bacteria.…”

“…White solid (250.2 mg, 92%). Mp 157-158 °C;1 H NMR (DMSO-d 6 ) δ 7.28 (m, 5H, Ar-H),3.55 (t, J 6.9 Hz, 2H, CH2N), 3.08 (t, J 6.4 Hz, 2H, CH2S), 2.06 (m, 2H, CH2);13 C NMR (DMSO-d6) δ 168.8, 138.8, 129.5, 126.9, 119.9, 43.9, 25.2, 24.5; HRMS (EI) for C10H12N2O3S2 [M + ] calcd: 272.0289; found: 272.0286. 1,3-Thiazin-2-ones (4b).…”