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. 10H-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.
journal_name
J Enzyme Inhib Med Chemjournal_title
Journal of enzyme inhibition and medicinal chemistryauthors
Morak-Młodawska B,Pluta K,Latocha M,Suwińska K,Jeleń M,Kuśmierz Ddoi
10.3109/14756366.2016.1151014subject
Has Abstractpub_date
2016-12-01 00:00:00pages
1512-9issue
6eissn
1475-6366issn
1475-6374journal_volume
31pub_type
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