3, 6-Diazaphenothiazines as potential lead molecules – synthesis, characterization and anticancer activity*. (1st November 2016)

• Record Type: Journal Article
• Authors: Morak-Młodawska, Beata; Pluta, Krystian; Latocha, Małgorzata; Suwińska, Kinga; Jeleń, Małgorzata; Kuśmierz, Dariusz
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 31:Number 6(2016:Dec.)
• Page Start: 1512
• Page End: 1519
• Publication Date: 2016-11-01
• Subjects: 2D NMR spectra -- anticancer activity -- gene expressions -- phenothiazines -- the Smiles rearrangement -- X-ray analysis; Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• DOI: 10.3109/14756366.2016.1151014
• Languages: English
• ISSNs: 1475-6366

Abstract

Abstract: 3, 6-Diazaphenothiazines were obtained in cyclization of 3-amino-3′-nitro-2, 4′-dipyridinyl sulfide and the reaction of sodium 3-amino-2-pyridinethiolate with 4-chloro-3-nitropyridine followed by alkylation and heteroarylation. The thiazine ring formation ran via the Smiles rearrangement. The structure elucidation was based on 2D NMR and X-ray analysis of N -methylated product. 3, 6-Diazaphenothiazines were investigated for antitumor activity using glioblastoma SNB-19, melanoma C-32 and breast cancer MCF-7 cells. 10 H -3, 6-diazaphenothiazine was 10 times more active (IC50 < 0.72 μg/mL) than cisplatin. Two diazaphenothiazines with the 2-pyrimidinyl and dimethylaminopropyl substituents were selectively active against MCF-7 and C-32 cells. The expressions of H3 (proliferation marker), TP53, CDKN1A (cell cycle regulators), BAX and BCL-2 (proapoptopic and antiapoptopic genes) were detected by RT-QPCR method. The expression analysis suggests the cell cycle arrest and the mitochondrial apoptosis pathway activation in MCF-7 and SNB-19 cells.