3,6-Diazaphenothiazines as potential lead molecules – synthesis, characterization and anticancer activity
PBN-AR
Instytucja
Wydział Matematyczno-Przyrodniczy.Szkoła Nauk Ścisłych (Uniwersytet Kardynała Stefana Wyszyńskiego w Warszawie)
Informacje podstawowe
Główny język publikacji
en
Czasopismo
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
ISSN
1475-6366
EISSN
Wydawca
INFORMA HEALTHCARE
DOI
URL
Rok publikacji
2016
Numer zeszytu
Strony od-do
1-8
Numer tomu
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
en
2D NMR spectra
X-ray analysis
anticancer activity
gene expressions
phenothiazines
the Smiles rearrangement
Streszczenia
Język
en
Treść
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 \textless 0.72 $μ$g/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.
Cechy publikacji
discipline:Chemia
discipline:Chemistry
Original article
Original article presents the results of original research or experiment.
Oryginalny artykuł naukowy
Oryginalny artykuł naukowy przedstawia rezultaty oryginalnych badań naukowych lub eksperymentu.
Inne
System-identifier
PBN-R:788650