Synthesis, spectroscopic characterization, and anticancer activity of new 10-substituted 1,6-diazaphenothiazines.
New phenothiazine derivatives as 10-substituted dipyridothiazines of the 1,6-diazaphenothiazine structure were obtained in the cyclization reaction of 3-amino-3'-nitro-2,2'-dipyridinyl sulfide and 3,3'-dinitro-2,2'-dipyridinyl disulfide, and in the reaction of 2-chloro-3-ntropyridine with sodium 3-amino-2-pyridinethiolate followed by various alkylation and arylation reactions. The reaction of the thiazine ring formation ran via the Smiles rearrangement of the S-N type. As the alkylation reactions could proceed at the thiazine, azine or both nitrogen atoms, the product structure elucidation was based on the 2D NMR (Rotating-frame Overhauser Effect Spectroscopy, Correlated Spectroscopy, Heteronuclear Single Quantum Coherence, and Heteronuclear Multiple Bond Correlation) spectra of theN-methylated product. Some 10-substituted 1,6-diazaphenothizines (5,10,12,13) were at least anticancer active against melanoma C-32 and breast cancer MCF-7 cell lines as a reference drug - cisplatin. The monoazaphenothiazine drug, prothipendyl, turned out to be less active than least 6 derivatives of the 1,6-diazaphenothiazine structure.
School of Pharmacy with the Division of Laboratory Medicine, Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, Sosnowiec, 41-200 Poland.
Beata
B
Morak-Młodawska
School of Pharmacy with the Division of Laboratory Medicine, Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, Sosnowiec, 41-200 Poland.
Krystian
K
Pluta
School of Pharmacy with the Division of Laboratory Medicine, Department of Cell Biology, The Medical University of Silesia, Jedności 8, Sosnowiec, 41-200 Poland.
Małgorzata
M
Latocha
School of Pharmacy with the Division of Laboratory Medicine, Department of Organic Chemistry, The Medical University of Silesia, Jagiellońska 4, Sosnowiec, 41-200 Poland.
Małgorzata
M
Jeleń
2D NMR spectra; Anticancer activity; Dipyridothiazines; NMR structure elucidation; Phenothiazines; The Smiles rearrangement